circRNA作用机制及其对动物肌肉发育的影响

doi:10.16431/j.cnki.1671-7236.2018.08.028

摘要/Abstract

摘要：

circRNA是一种不具有5'端帽子结构和3'端多聚（A）尾巴结构但能稳定存在于真核细胞内的非编码RNA（ncRNA），是经过反向剪接构成的闭合环状分子，为近年来的研究热点。越来越多的研究已证明，circRNA对生物体的各种生命活动发挥着极其重要的调控作用。根据组成不同，circRNA可分为外显子环状、内含子环状及内含子外显子共同组成的环状。同时circRNA功能的发挥依赖于其细胞定位，位于细胞核的circRNA主要在基因转录水平与RNA聚合酶Ⅱ结合调控寄主基因的转录活性；而位于细胞液中的circRNA主要发挥竞争性内源RNA的作用，通过竞争性抑制miRNA与靶基因mRNA 3'UTR的结合，发挥其对miRNA和靶基因的调控作用；circRNA还可翻译成蛋白质或多肽。目前，circRNA在畜禽肌肉生长发育方面的相关研究还处于起步阶段，主要是关于circRNA作为竞争性内源RNA发挥重要调控功能。文章就circRNA的发现、分类、生成机制、作用方式及对动物肌细胞增殖和分化的前沿研究作一简要阐述，并提出circRNA对畜禽肌肉功能研究的展望，以期为今后circRNA相关功能的研究提供参考。

关键词: circRNA; 产生机制; 作用方式; 肌肉

Abstract:

circRNA is a non-coding RNA (ncRNA) that does not have a 5' end cap structure and 3' end poly (A) tail structure but can stably exist in eukaryotic cells.circRNA that formed by reverse splicing is the hottest ncRNA in the past few years.Much more researches have proved that circRNA plays an extremely important regulatory roles in the life activities of organisms.According to the different composition,circRNA can be divided into exon candidates,intron candidates and candidates of the intron-exons.In addition,the function of circRNA depended on its cellular site-specification.circRNA located in the nucleus always regulates the transcriptional activity of hosting genes mainly at gene transcriptional level with RNA polymerase Ⅱ;circRNA in the cytoplasm plays a major function in the role of competitive endogenous RNA,and mainly competitive inhibition of miRNA and their target 3'UTR to regulate the expression levels of miRNA and their targets;Recent studies have shown that circRNA can also be translated into proteins or peptides.At present,the related circRNA research on animal muscle growth and development is still at the initial stage,and the related research is mainly about circRNA as a competitive endogenous RNA to play an important regulatory role.This paper summarized the discovery,classification,production mechanism,mode of action of circRNA and its effect on myocyte proliferation and differentiation in recent years.Finally,we proposed a prospective study of circRNA on muscle growth and development,and we hope our research could offer some useful experience for other researches.

Key words: circRNA; generation mechanism; mode of action; muscle

中图分类号:

S813

谢月琴, 陈婷, 罗君谊, 习欠云, 张永亮, 孙加节. circRNA作用机制及其对动物肌肉发育的影响[J]. 《中国畜牧兽医》, 2018, 45(8): 2270-2275.

XIE Yueqin, CHEN Ting, LUO Junyi, XI Qianyun, ZHANG Yongliang, SUN Jiajie. Mechanism of circRNA and Its Effect on Development of Animal Muscles[J]. , 2018, 45(8): 2270-2275.

参考文献

[1] SANGER H L,KLOTZ G,RIESNER D,et al.Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures[J].Proceedings of the National Academy of Sciences,1976,73(11):3852-3856.
[2] MATSUMOTO Y,FISHEL R,WICKNER R B.Circular single-stranded RNA replicon in Saccharomyces cerevisiae[J].Proceedings of the National Academy of Sciences,1990,87(19):7628-7632.
[3] CAPEL B,SWAIN A,NICOLIS S,et al.Circular transcripts of the testis-determining gene Sry in adult mouse testis[J].Cell,1993,73(5):1019-1030.
[4] BURD C E,JECK W R,LIU Y,et al.Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk[J]. PLoS Genetics,2010,6(12):e1001233.
[5] DANAN M,SCHWARTZ S,EDELHEIT S,et al.Transcriptome-wide discovery of circular RNAs in Archaea[J].Nucleic Acids Research,2011,40(7):3131-3142.
[6] ABDELMOHSEN K,PANDA A C,DE S,et al.Circular RNAs in monkey muscle:Age-dependent changes[J].Aging (Albany NY),2015,7(11):903-910.
[7] VENØ M T,HANSEN T B,VENØ S T,et al.Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development[J].Genome Biology,2015,16(1):245-261.
[8] LI Y,ZHENG Q,BAO C,et al.Circular RNA is enriched and stable in exosomes:A promising biomarker for cancer diagnosis[J].Cell Research,2015,25(8):981-984.
[9] AMBROS V,BARTEL B,BARTEL D P,et al.A uniform system for microRNA annotation[J]. RNA,2003,9(3):277-279.
[10] PETKOVIC S,MVLLER S.RNA circularization strategies in vivo and in vitro[J].Nucleic Acids Research,2015,43(4):2454-2465.
[11] COCQUERELLE C,MASCREZ B,HETUIN D,et al.Mis-splicing yields circular RNA molecules[J].FASEB Journal,1993,7(1):155-160.
[12] ZAPHIROPOULOS P G.Circular RNAs from transcripts of the rat cytochrome P4502C24 gene:Correlation with exon skipping[J].Proceedings of the National Academy of Sciences of the United States of America,1996,93(13):6536-6541.
[13] ZAPHIROPOULOS P G.Exon skipping and circular RNA formation in transcripts of the human cytochrome P-4502C18 gene in epidermis and of the rat androgen binding protein gene in testis[J].Molecu-lar & Cellular Biology,1997,17(6):2985-2993.
[14] STARKE S,JOST I,ROSSBACH O,et al.Exon circularization requires canonical splice signals[J].Cell Reports,2015,10(1):103-111.
[15] ZHANG Y,ZHANG X O,CHEN T,et al.Circular intronic noncoding RNAs[J].Molecular Cell,2013,51(6):792-806.
[16] JECK W R,SORRENTINO J A,WANG K,et al.Circular RNAs are abundant,conserved,and associated with ALU repeats[J].RNA,2013,19(2):141-157.
[17] LI Z,HUANG C,BAO C,et al.Exon-intron circular RNAs regulate transcription in the nucleus[J].Nature Structural & Molecular Biology,2015,22(3):256-264.
[18] CHEN L L.The biogenesis and emerging roles of circular RNAs[J].Nature Reviews Molecular Cell Biology,2016,17(4):205-211.
[19] BAI Y,ZHANG Y,HAN B,et al.Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integ-rity[J].Journal of Neuroscience,2017,38(1):32-50.
[20] CHEN J,CUI L,YUAN J,et al.Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124[J].Biochemical and Biophysical Research Communications,2017,494(1-2):126-132.
[21] LI H,YANG J,WEI X,et al.CircFUT10 reduces proliferation and facilitates differentiation of myoblasts by sponging miR-133a[J].Journal of Cellular Physiology,2018,233(6):4643-4651.
[22] LI G,TANG H,LIU P,et al.circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a[J].Journal of Experimental & Clinical Cancer Research,2017,36(1):145-156.
[23] TAO H,XIONG Q,ZHANG F,et al.Circular RNA profiling reveals chi_circ_0008219 function as microRNA sponges in pre-ovulatory ovarian follicles of goats (Capra hircus)[J]. Genomics,2018,110(4):257-266.
[24] WANG G,LIU H,ZHANG J,et al.Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression[J].Molecular Cancer,2017,16(1):151-166.
[25] ZHANG H,WANG G,DING C,et al.Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression[J].Oncotarget,2017,8(37):61687-61697.
[26] KOS A,DIJKEMA R,ARNBERG A C,et al.The hepatitis deltavirus possesses a circular RNA[J].Nature,1986,323(6088):558-560.
[27] ABOUHAIDAR M G,VENKATARAMAN S,GOLSHANI A,et al.Novel coding,translation,and gene expression of a replicating covalently closed circular RNA of 220 nt[J].Proceedings of the National Academy of Sciences,2014,111(40):14542-14547.
[28] PERRIMAN R,ARES M.Circular mRNA can direct translation of extremely long repeating-sequence proteins in vivo[J].RNA,1998,4(9):1047-1054.
[29] YANG Y,FAN X,MAO M,et al.Extensive translation of circular RNAs driven by N6-methylade-nosine[J].Cell Research,2017,27(5):626-641.
[30] PAMUDURTI N R,BARTOK O,JENS M,et al.Translation of circRNAs[J].Molecular Cell,2017,66(1):9-21.
[31] LEGNINI I,DI TIMOTEO G,ROSSI F,et al.Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis[J].Molecular Cell,2017,66(1):22-37.
[32] YANG Y,GAO X,ZHANG M,et al.Novel role of FBXW7 circular RNA in repressing glioma tumorigenesis[J].Journal of the National Cancer Institute,2018,110(3):304-315.
[33] RUDNICKI M A,BRAUN T,HINUMA S,et al.Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development[J]. Cell,1992,71(3):383-390.
[34] HADJIARGYROU M.Mustn1:A developmentally regulated pan-musculoskeletal cell marker and regulatory gene[J].International Journal of Molecular Sciences,2018,19(1):206-226.
[35] AL-SHANTI N,STEWART C E.Ca²⁺/calmodulin-dependent transcriptional pathways:Potential mediators of skeletal muscle growth and development[J].Biological Reviews,2009,84(4):637-652.
[36] MARKLJUNG E,JIANG L,JAFFE J D,et al.ZBED6,a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth[J].PLoS Biology,2009,7(12):e1000256.
[37] CHEN J F,MANDEL E M,THOMSON J M,et al.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation[J].Nature Genetics,2006,38(2):228-233.
[38] OUYANG H,CHEN X,WANG Z,et al.Circular RNAs are abundant and dynamically expressed during embryonic muscle development in chickens[J].DNA Research,2017,25(1):71-86.
[39] WEI X,LI H,YANG J,et al.Circular RNA profiling reveals an abundant circLMO7 that regulates myoblasts differentiation and survival by sponging miR-378a-3p[J].Cell Death & Disease,2017,8(10):e3153.
[40] QIAN D Y,YAN G B,BAI B,et al.Differential circRNA expression profiles during the BMP2-induced osteogenic differentiation of MC3T3-E1 cells[J].Biomedicine & Pharmacotherapy,2017,90:492-499.
[41] LI C,LI X,YAO Y,et al.Genome-wide analysis of circular RNAs in prenatal and postnatal muscle of sheep[J].Oncotarget,2017,8(57):97165-97177.
[42] LIANG G,YANG Y,NIU G,et al.Genome-wide profiling of Sus scrofa circular RNAs across nine organs and three developmental stages[J].DNA Research,2017,24(5):523-535.