The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protei...The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protein translation,namely,messenger RNAs(mRNAs)as temporary copies of genetic information,ribosomal RNAs(rRNAs)as a main component of ribosome,or translators of codon sequence(t RNAs).The statistical reality,however,is that these processes account for less than 2%of the genome,and insufficiently explain the functionality of 98%of transcribed RNAs.Recent discoveries have unveiled thousands of unique non-coding RNAs(ncRNAs)and shifted the perception of them from being"junk"transcriptional products to"yet to be elucidated"—and potentially monumentally important—RNAs.Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates.In major cancers,ncRNAs have been identified as both oncogenic drivers and tumor suppressors,indicating a complex regulatory network among these ncRNAs.Herein,we provide a comprehensive review of the various ncRNAs and their functional roles in cancer,and the pre-clinical and clinical development of nc RNA-based therapeutics.A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics.展开更多
Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.H...Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.展开更多
Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC...Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.展开更多
Circular RNAs(circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, bind...Circular RNAs(circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, binding mi RNAs or proteins, and being translated into proteins, which are important for cell proliferation and cell differentiation, individual growth and development, as well as many other biological processes. However, compared with that in animal models, studies of circRNAs in plants lags behind and,particularly, the regulatory mechanisms of biogenesis and molecular functions of plant circRNAs remain elusive. Recent studies have shown that circRNAs are wide spread in plants with tissue-or developmentspecific expression patterns and are responsive to a variety of environmental stresses. In this review, we summarize these advances, focusing on the regulatory mechanisms of biogenesis, molecular and biological functions of circRNAs, and the methods for investigating circRNAs. We also discuss the challenges and the prospects of plant circ RNA studies.展开更多
Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of ...Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of circ RNAs in bladder cancer（BC） and the molecular mechanisms have yet to be fully understood. In this study, the clinical specimens were obtained and the expression level of a circ RNA BCRC4 was detected by real-time PCR in both BC tissues and cell line. The circular RNA over-expression plasmid was constructed and transfected into BC cells and related cell line. The cell cycles and apoptosis were observed using inverted microscope and flow cytometry. Western blotting was used to compare the relative protein expression of groups with different treatments. It was found that circ RNA BCRC4 expression was lower in BC tissues than in adjacent normal tissues. Furthermore, consequences of forced-expression of BCRC4 promoted apoptosis and inhibited viability of T24T and UMUC3 cells, and up-regulated BCRC4-increased miR-101 level, which suppressed EZH2 expression in both RNA and protein levels. In addition, gambogic acid（GA） is a promising natural anticancer compound for BC therapy, and GA treatment increased the BCRC4 expression in T24T and UMUC3 cells in a dose-dependent manner. Altogether, our findings suggest that BCRC4 functions as a tumor suppressor in BC, and mediates anticancer function, at least in part, by up-regulating the expression of miR-101. Targeting this newly identified circ RNA may help us develop a novel strategy for treating human BC.展开更多
基金supported by grants from the National Key Research and Development Program of China(2016YFC1302300)the National Natural Science Foundation of China(81621004,81720108029,81930081,91940305,81874226 and 81803020)+2 种基金Guangdong Science and Technology Department(2017B030314026)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)Guangzhou Science Technology and Innovation Commission(201803040015)partly supported by Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation。
文摘The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protein translation,namely,messenger RNAs(mRNAs)as temporary copies of genetic information,ribosomal RNAs(rRNAs)as a main component of ribosome,or translators of codon sequence(t RNAs).The statistical reality,however,is that these processes account for less than 2%of the genome,and insufficiently explain the functionality of 98%of transcribed RNAs.Recent discoveries have unveiled thousands of unique non-coding RNAs(ncRNAs)and shifted the perception of them from being"junk"transcriptional products to"yet to be elucidated"—and potentially monumentally important—RNAs.Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates.In major cancers,ncRNAs have been identified as both oncogenic drivers and tumor suppressors,indicating a complex regulatory network among these ncRNAs.Herein,we provide a comprehensive review of the various ncRNAs and their functional roles in cancer,and the pre-clinical and clinical development of nc RNA-based therapeutics.A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics.
基金Supported by grants to G. S.: the National Key R&D Program of China (2019YFA0802600 and 2018YFC1004500)the National Natural Science Foundation of China (31725016, 31930019, and 91940303)and the Strategic Priority Research Program (Pilot Study) “Biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (XDPB10).
文摘Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.
文摘Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.
基金supported by grants of Key project of intergovernmental International Science and Technology Innovation Cooperation, MOST of China (2022YFE0100500)the National Key Laboratory of Crop Genetic Improvement Self-research Program (ZW18B0102)。
文摘Circular RNAs(circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, binding mi RNAs or proteins, and being translated into proteins, which are important for cell proliferation and cell differentiation, individual growth and development, as well as many other biological processes. However, compared with that in animal models, studies of circRNAs in plants lags behind and,particularly, the regulatory mechanisms of biogenesis and molecular functions of plant circRNAs remain elusive. Recent studies have shown that circRNAs are wide spread in plants with tissue-or developmentspecific expression patterns and are responsive to a variety of environmental stresses. In this review, we summarize these advances, focusing on the regulatory mechanisms of biogenesis, molecular and biological functions of circRNAs, and the methods for investigating circRNAs. We also discuss the challenges and the prospects of plant circ RNA studies.
文摘Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of circ RNAs in bladder cancer（BC） and the molecular mechanisms have yet to be fully understood. In this study, the clinical specimens were obtained and the expression level of a circ RNA BCRC4 was detected by real-time PCR in both BC tissues and cell line. The circular RNA over-expression plasmid was constructed and transfected into BC cells and related cell line. The cell cycles and apoptosis were observed using inverted microscope and flow cytometry. Western blotting was used to compare the relative protein expression of groups with different treatments. It was found that circ RNA BCRC4 expression was lower in BC tissues than in adjacent normal tissues. Furthermore, consequences of forced-expression of BCRC4 promoted apoptosis and inhibited viability of T24T and UMUC3 cells, and up-regulated BCRC4-increased miR-101 level, which suppressed EZH2 expression in both RNA and protein levels. In addition, gambogic acid（GA） is a promising natural anticancer compound for BC therapy, and GA treatment increased the BCRC4 expression in T24T and UMUC3 cells in a dose-dependent manner. Altogether, our findings suggest that BCRC4 functions as a tumor suppressor in BC, and mediates anticancer function, at least in part, by up-regulating the expression of miR-101. Targeting this newly identified circ RNA may help us develop a novel strategy for treating human BC.
