The let-7 miRNAwas one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. e...The let-7 miRNAwas one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the ＇seed sequence＇ and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase Ⅱ and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in ver- tebrates, such as the mouse and the human.展开更多
Small RNAs(sRNAs) are vital regulators of gene expression and involved in various biological processes. Among them, micro RNAs(mi RNAs) and phased small interfering RNAs(phasi RNAs) have been well defined and studied ...Small RNAs(sRNAs) are vital regulators of gene expression and involved in various biological processes. Among them, micro RNAs(mi RNAs) and phased small interfering RNAs(phasi RNAs) have been well defined and studied in the past decades. A bunch of scripts or pipelines were developed to annotate mi RNAs and phasi RNAs. However, some computational annotations are rough and without careful manual check,resulting in low quality annotation. In this study, 19 public strawberry(Fragaria vesca) s RNA sequencing data from nine different tissues were collected to annotate mi RNAs and PHAS loci in F. vesca. After bioinformatics analysis and careful manual checking, 167 known mi RNAs, 27 mi RNA*s with notable abundance, 54 novel mi RNAs were accurately annotated. The terms of two mi RNAs were corrected from mi R477 b and mi R5225 using mi RN47 and mi R3627 h, respectively. Besides 21 nucleotides(nt) mi R390, eleven mi RNAs with a length of 22-nt are in charge of triggering the biogenesis of 21-nt phasi RNAs from 110 PHAS loci in strawberry. In particular, we found several PHAS loci were targeted by two different mi RNAs(similar to the "two-hit" model) and the phasi RNA generating region located between two target sites. We speculate that one target site is in control of triggering phasi RNA biogenesis and the other target site define the boundary of the region of phasi RNA biogenesis,which likely provide an accurate way for phasi RNA generation. Overall, we provided a comprehensive and accurate annotation of mi RNAs and PHAS loci in the F. vesca genome.展开更多
MicroRNAs（miRNAs） are a class of about 20—24 nt small non-coding RNAs that can regulate their target gene expression transcriptionally and posttranscriptionally.There are an increasing number of studies describing ...MicroRNAs（miRNAs） are a class of about 20—24 nt small non-coding RNAs that can regulate their target gene expression transcriptionally and posttranscriptionally.There are an increasing number of studies describing the identification of new components and regulatory mechanisms involved in the miRNA biogenesis and effector pathway as well as new functions of miRNAs in plant development. This review mainly focuses on the components involved in this pathway,and the developmental defects associated with the corresponding mutations.Some functions of important miRNAs in plant development,together with the modes of miRNA action,are also discussed in this review to describe the recent advance in this area.展开更多
Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sour...Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sources:The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science.Study selection:The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.Results:CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases.Conclusions:Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.展开更多
Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved...Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.展开更多
MicroRNAs （miRNAs） are endogenously expressed non-coding RNAs of 20-24 nucleotides, which post-transcriptionally regulate gene expression in plants and animals. Recently it has been recognized that miRNAs comprise o...MicroRNAs （miRNAs） are endogenously expressed non-coding RNAs of 20-24 nucleotides, which post-transcriptionally regulate gene expression in plants and animals. Recently it has been recognized that miRNAs comprise one of the abundant gene families in multicellular species, and their regulatory functions in various biological processes are widely spread. There has been a surge in the research activities in this field in the past few years. From the very beginning, computational methods have been utilized as indispensable tools, and many discoveries have been obtained through combination of experimental and computational approaches. In this review, both biological and computational aspects of miRNA will be discussed. A brief history of the discovery of miRNA and discussion of microarray applications in miRNA research are also included.展开更多
Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria...Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further study.Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology.In this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage cells.Therefore,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development.The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.展开更多
Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistan...Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.展开更多
MicroRNAs （miRNAs） are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly contr...MicroRNAs （miRNAs） are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs （pre-miRNAs） from the nucleus to the cytoplasm by exportin-5 （XPO5）. Given the critical role of nuclear export of premiRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis. Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pinl impair XPO5＇s nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma. In this review, we focus on how XPO5 transports pre-miRNAs in the cells and summarize the dysregnlation of XPO5 in human tumors.展开更多
Plant prevacuolar compartments （PVCs）, or multivesicular bodies （MVBs）, are single membrane-bound organelles that play important roles in mediating protein trafficking to vacuoles in the secretory pathway. PVC/MVB...Plant prevacuolar compartments （PVCs）, or multivesicular bodies （MVBs）, are single membrane-bound organelles that play important roles in mediating protein trafficking to vacuoles in the secretory pathway. PVC/MVB also serves as a late endosome in the endocytic pathway in plants. Since the plant PVC was iden- tified as an MVB more than 10 years ago,-great progress has been made toward the understanding of PVC/ MVB function and biogenesis in plants. In this review, we first summarize previous research into the iden- tification and characterization of plant PVCs/MVBs, and then highlight recent advances on the mechanisms underlying intraluminal vesicle formation and maturation of plant PVCs/MVBs. In addition, we discuss the possible crosstalk that appears to occur between PVCs/MVBs and autophagosomes during autophagy in plants. Finally, we list some open questions and present future perspectives in this field.展开更多
文摘The let-7 miRNAwas one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the ＇seed sequence＇ and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase Ⅱ and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in ver- tebrates, such as the mouse and the human.
基金supported by the National Natural Science Foundation of China(Grant No.31872063)。
文摘Small RNAs(sRNAs) are vital regulators of gene expression and involved in various biological processes. Among them, micro RNAs(mi RNAs) and phased small interfering RNAs(phasi RNAs) have been well defined and studied in the past decades. A bunch of scripts or pipelines were developed to annotate mi RNAs and phasi RNAs. However, some computational annotations are rough and without careful manual check,resulting in low quality annotation. In this study, 19 public strawberry(Fragaria vesca) s RNA sequencing data from nine different tissues were collected to annotate mi RNAs and PHAS loci in F. vesca. After bioinformatics analysis and careful manual checking, 167 known mi RNAs, 27 mi RNA*s with notable abundance, 54 novel mi RNAs were accurately annotated. The terms of two mi RNAs were corrected from mi R477 b and mi R5225 using mi RN47 and mi R3627 h, respectively. Besides 21 nucleotides(nt) mi R390, eleven mi RNAs with a length of 22-nt are in charge of triggering the biogenesis of 21-nt phasi RNAs from 110 PHAS loci in strawberry. In particular, we found several PHAS loci were targeted by two different mi RNAs(similar to the "two-hit" model) and the phasi RNA generating region located between two target sites. We speculate that one target site is in control of triggering phasi RNA biogenesis and the other target site define the boundary of the region of phasi RNA biogenesis,which likely provide an accurate way for phasi RNA generation. Overall, we provided a comprehensive and accurate annotation of mi RNAs and PHAS loci in the F. vesca genome.
基金supported by a start-up fund from Zhejiang Agriculture & Forestry University(No.2034020060)the grants from the 1000 Youth Talents Program in China(No. 2034020065)the National Natural Science Foundation of China(No.2045210147)
文摘MicroRNAs（miRNAs） are a class of about 20—24 nt small non-coding RNAs that can regulate their target gene expression transcriptionally and posttranscriptionally.There are an increasing number of studies describing the identification of new components and regulatory mechanisms involved in the miRNA biogenesis and effector pathway as well as new functions of miRNAs in plant development. This review mainly focuses on the components involved in this pathway,and the developmental defects associated with the corresponding mutations.Some functions of important miRNAs in plant development,together with the modes of miRNA action,are also discussed in this review to describe the recent advance in this area.
文摘Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sources:The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science.Study selection:The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.Results:CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases.Conclusions:Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.
文摘Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.
文摘MicroRNAs （miRNAs） are endogenously expressed non-coding RNAs of 20-24 nucleotides, which post-transcriptionally regulate gene expression in plants and animals. Recently it has been recognized that miRNAs comprise one of the abundant gene families in multicellular species, and their regulatory functions in various biological processes are widely spread. There has been a surge in the research activities in this field in the past few years. From the very beginning, computational methods have been utilized as indispensable tools, and many discoveries have been obtained through combination of experimental and computational approaches. In this review, both biological and computational aspects of miRNA will be discussed. A brief history of the discovery of miRNA and discussion of microarray applications in miRNA research are also included.
基金Supported by The National Science Council,Taiwan,China,and Changhua Christian Hospital
文摘Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further study.Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology.In this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage cells.Therefore,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development.The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.
基金supported by the National Institutes of Health through The University of Texas MD Anderson Cancer Center’s Support Grant CA016672National Cancer Institute grant RO1CA 089266 (MHL)+3 种基金Directed Medical Research Programs Department of Defense Synergistic Idea Development Award BC062166 (SCY, MHL)the Susan G.Komen Breast Cancer Research Foundation Promise Grant KG081048 (SCY, MHL)Vietnam Education Foundation, Rosalie B.Hite FoundationDepartment of Defense Breast Cancer Research Program (Award # W81XWH-10-0171)
文摘Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.81572739 and 81772960)
文摘MicroRNAs （miRNAs） are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs （pre-miRNAs） from the nucleus to the cytoplasm by exportin-5 （XPO5）. Given the critical role of nuclear export of premiRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis. Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pinl impair XPO5＇s nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma. In this review, we focus on how XPO5 transports pre-miRNAs in the cells and summarize the dysregnlation of XPO5 in human tumors.
文摘Plant prevacuolar compartments （PVCs）, or multivesicular bodies （MVBs）, are single membrane-bound organelles that play important roles in mediating protein trafficking to vacuoles in the secretory pathway. PVC/MVB also serves as a late endosome in the endocytic pathway in plants. Since the plant PVC was iden- tified as an MVB more than 10 years ago,-great progress has been made toward the understanding of PVC/ MVB function and biogenesis in plants. In this review, we first summarize previous research into the iden- tification and characterization of plant PVCs/MVBs, and then highlight recent advances on the mechanisms underlying intraluminal vesicle formation and maturation of plant PVCs/MVBs. In addition, we discuss the possible crosstalk that appears to occur between PVCs/MVBs and autophagosomes during autophagy in plants. Finally, we list some open questions and present future perspectives in this field.
