In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukary...In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'- UTRs of most eukaryotic mRNAs. Combined with other initiation factors, elF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the elF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E.展开更多
Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75...Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.展开更多
Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the ...Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment.However,most of our understanding of stress granules are still in the stage of molecular and cell biology,and a transitional gap for its actual effect on clinical settings remains.In this review,we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy,using breast cancer as an example.展开更多
The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Ki...The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Kip1 protein has dual roles for both cancer prevention and promotion. For example, numerous nutritional and chemopreventive anti-cancer agents specifically increase the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. On the other hand, pro-cancer agents (like glucose, insulin and other growth factors frequently seen in obesity and/or diabetes) specifically decrease the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. Unlike expression of any other cell cycle regulatory proteins, expression of p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long and unusual 5’-untranslated region (from -575 to -1 in human). It appears that the 5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agents are added and another decrease the expression of p27K1p1 when pro-cancer agents are added. For this short concept proposal, Dr. Albert Einstein’s “visualized thought experiments (German: Gedanken experiment)” were used as a fundamental tool for understanding how either anti- or pro-cancer agents bring the primary structure of the 5’-untranslated region of p27Kip1 mRNA into two alternative secondary structures, thereby either increasing or decreasing, respectively, the translation initiation of p27Kip1 protein.展开更多
Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The ...Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin(mTOR) complexes.This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs.Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation.Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses.展开更多
The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neuro...The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.展开更多
Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or ty...Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.展开更多
AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotti...AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.展开更多
tRNA-derived small RNAs(tsRNAs)are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases.However,their exact presence and function in hepatocellular carcinoma(HCC)remain unclear...tRNA-derived small RNAs(tsRNAs)are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases.However,their exact presence and function in hepatocellular carcinoma(HCC)remain unclear.Here,differentially expressed tsRNAs in HCC were profiled.A novel tsRNA,tRNAGln-TTG derived 5′-tiRNA-Gln,is significantly downregulated,and its expression level is correlated with progression in patients.In HCC cells,5′-tiRNA-Gln overexpression impaired the proliferation,migration,and invasion in vitro and in vivo,while 5′-tiRNA-Gln knockdown yielded opposite results.5′-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I(EIF4A1),which unwinds complex RNA secondary structures during translation initiation,causing the partial inhibition of translation.The suppressed downregulated proteins include ARAF,MEK1/2 and STAT3,causing the impaired signaling pathway related to HCC progression.Furthermore,based on the construction of a mutant 5′-tiRNA-Gln,the sequence of forming intramolecular G-quadruplex structure is crucial for 5′-tiRNA-Gln to strongly bind EIF4A1 and repress translation.Clinically,5′-tiRNA-Gln expression level is negatively correlated with ARAF,MEK1/2,and STAT3 in HCC tissues.Collectively,these findings reveal that 5′-tiRNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular Gquadruplex structure,and this process partially inhibits translation and HCC progression.展开更多
Translation initiation sites (TISs) are important signals in cDNA sequences. In many previous attempts to predict TISs in cDNA sequences, three major factors affect the prediction performance: the nature of the cDNA s...Translation initiation sites (TISs) are important signals in cDNA sequences. In many previous attempts to predict TISs in cDNA sequences, three major factors affect the prediction performance: the nature of the cDNA sequence sets, the rel- evant features selected, and the classification methods used. In this paper, we examine different approaches to select and integrate relevant features for TIS pre- diction. The top selected significant features include the features from the position weight matrix and the propensity matrix, the number of nucleotide C in the se- quence downstream ATG, the number of downstream stop codons, the number of upstream ATGs, and the number of some amino acids, such as amino acids A and D. With the numerical data generated from these features, different classifi- cation methods, including decision tree, naive Bayes, and support vector machine, were applied to three independent sequence sets. The identified significant features were found to be biologically meaningful, while the experiments showed promising results.展开更多
Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis require...Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis requires host cellular factors for translating their viral RNAs, and for regulating their replication and cell to cell systemic movement. Therefore, the viruses are dependent on cellular translation factors. Mutations in the gene encoding eIF4E and eIF4G or their isoforms, eIFiso4 E, eIFiso4 G and eIF2Bβ have been mapped as a source of plant potyvirus while other genus of plant virus recessive resistance genes in many species are originated from these loci. Some of other plant translation factors, such as eIF3,eIF4 A-like helicases, eEF1A and eEF1B, which are required in interacting with viral RNAs and regulating various aspects of the infection cycle,have also been identified. Here, we summarized the mechanisms utilized by RNA viruses of eukaryotic plants and the essential roles of e IFs in virus infection. Moreover, we discussed the potential of e IFs as a target gene in the development of genetic resistance to viruses for crop improvement. This review highlighted newly revealed examples of abnormal translational strategies and provided insights into natural host resistance mechanisms that have been linked to 3 cap-independent translational enhancer activity.展开更多
文摘In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'- UTRs of most eukaryotic mRNAs. Combined with other initiation factors, elF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the elF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E.
基金supported by the National Key Research and Development Plan(SQ2016YFSF110100,2016YFC0905000)National Natural Science Foundation(81373490,81573508,81573463)+1 种基金Hunan Provincial Science and Technology Plan(2015JC3025)Open Foundation of Innovative Platform in University of Hunan Province(421530004),China
基金supported by the National Basic Research Program of China(2007CB512900)
文摘Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.
基金This work was supported by the National Natural Science Foundation of China(No.82002979 and 81702839)the Scientific Research and Development Funds of Peking Uni・versity People's Hospital,China(No.RDY2020-16).
文摘Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment.However,most of our understanding of stress granules are still in the stage of molecular and cell biology,and a transitional gap for its actual effect on clinical settings remains.In this review,we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy,using breast cancer as an example.
文摘The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Kip1 protein has dual roles for both cancer prevention and promotion. For example, numerous nutritional and chemopreventive anti-cancer agents specifically increase the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. On the other hand, pro-cancer agents (like glucose, insulin and other growth factors frequently seen in obesity and/or diabetes) specifically decrease the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. Unlike expression of any other cell cycle regulatory proteins, expression of p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long and unusual 5’-untranslated region (from -575 to -1 in human). It appears that the 5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agents are added and another decrease the expression of p27K1p1 when pro-cancer agents are added. For this short concept proposal, Dr. Albert Einstein’s “visualized thought experiments (German: Gedanken experiment)” were used as a fundamental tool for understanding how either anti- or pro-cancer agents bring the primary structure of the 5’-untranslated region of p27Kip1 mRNA into two alternative secondary structures, thereby either increasing or decreasing, respectively, the translation initiation of p27Kip1 protein.
基金Supported by National Institute of Health Grants R37 AA-011290and DK-072909
文摘Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin(mTOR) complexes.This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs.Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation.Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses.
基金supported by the National Natural Science Foundation of China,Nos.30772368(to DH),81371034(to XH)the Key Project of Natural Science Foundation of Shaanxi Province,No.2017JZ025(to DH).
文摘The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.
文摘Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.
文摘AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.
基金generously supported by the National Natural Science Foundation of China(Nos.82072650 and 81902405)Key Research and Development Program of Zhejiang Province(No.2021C03121)+1 种基金2019 Liver Cancer Diagnosis and Treatment Communication Fund(No.CXPJJH11900009-12)Grant from Health Commission of Zhejiang Province(No.JBZX-202004).
文摘tRNA-derived small RNAs(tsRNAs)are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases.However,their exact presence and function in hepatocellular carcinoma(HCC)remain unclear.Here,differentially expressed tsRNAs in HCC were profiled.A novel tsRNA,tRNAGln-TTG derived 5′-tiRNA-Gln,is significantly downregulated,and its expression level is correlated with progression in patients.In HCC cells,5′-tiRNA-Gln overexpression impaired the proliferation,migration,and invasion in vitro and in vivo,while 5′-tiRNA-Gln knockdown yielded opposite results.5′-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I(EIF4A1),which unwinds complex RNA secondary structures during translation initiation,causing the partial inhibition of translation.The suppressed downregulated proteins include ARAF,MEK1/2 and STAT3,causing the impaired signaling pathway related to HCC progression.Furthermore,based on the construction of a mutant 5′-tiRNA-Gln,the sequence of forming intramolecular G-quadruplex structure is crucial for 5′-tiRNA-Gln to strongly bind EIF4A1 and repress translation.Clinically,5′-tiRNA-Gln expression level is negatively correlated with ARAF,MEK1/2,and STAT3 in HCC tissues.Collectively,these findings reveal that 5′-tiRNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular Gquadruplex structure,and this process partially inhibits translation and HCC progression.
基金This research was supported by Research Grant No.BM/00/007 from the Biomedical Research Council(BMRC)of the Agency for Science,Technology,and Research(A*Star)and the Ministry of Education in Singapore.
文摘Translation initiation sites (TISs) are important signals in cDNA sequences. In many previous attempts to predict TISs in cDNA sequences, three major factors affect the prediction performance: the nature of the cDNA sequence sets, the rel- evant features selected, and the classification methods used. In this paper, we examine different approaches to select and integrate relevant features for TIS pre- diction. The top selected significant features include the features from the position weight matrix and the propensity matrix, the number of nucleotide C in the se- quence downstream ATG, the number of downstream stop codons, the number of upstream ATGs, and the number of some amino acids, such as amino acids A and D. With the numerical data generated from these features, different classifi- cation methods, including decision tree, naive Bayes, and support vector machine, were applied to three independent sequence sets. The identified significant features were found to be biologically meaningful, while the experiments showed promising results.
基金The authors thank Mr.Tomas Maher from the Department of Biology at the Pennsylvania State University for language editing.This work is supported by the National Natural Science Foundation of Zhejiang Province(Grant No.LZ20C150002)and the National Natural Science Foundation of China(Grant No.31872095).
文摘Viruses are representative of a global threat to agricultural production. Genetic resistance is the preferred strategy for the control of viral infection and against loss of crop yield. Viral protein synthesis requires host cellular factors for translating their viral RNAs, and for regulating their replication and cell to cell systemic movement. Therefore, the viruses are dependent on cellular translation factors. Mutations in the gene encoding eIF4E and eIF4G or their isoforms, eIFiso4 E, eIFiso4 G and eIF2Bβ have been mapped as a source of plant potyvirus while other genus of plant virus recessive resistance genes in many species are originated from these loci. Some of other plant translation factors, such as eIF3,eIF4 A-like helicases, eEF1A and eEF1B, which are required in interacting with viral RNAs and regulating various aspects of the infection cycle,have also been identified. Here, we summarized the mechanisms utilized by RNA viruses of eukaryotic plants and the essential roles of e IFs in virus infection. Moreover, we discussed the potential of e IFs as a target gene in the development of genetic resistance to viruses for crop improvement. This review highlighted newly revealed examples of abnormal translational strategies and provided insights into natural host resistance mechanisms that have been linked to 3 cap-independent translational enhancer activity.