环状RNA在羊重要经济性状中的应用研究

doi:10.16431/j.cnki.1671-7236.2025.06.002

摘要/Abstract

摘要： 环状RNA(circular RNA，circRNA)是一种新型的RNA分子，是由前体mRNA通过反向剪接形成共价闭合的环状结构，由于缺少帽子结构和PolyA尾巴使其稳定且不易被核酸外切酶降解。随着高通量测序和生物信息技术的快速发展，解释了许多circRNA在动植物生命活动和疾病发生中的重要调控功能，如竞争性结合微小RNA(microRNA，miRNA)、调控基因转录、编码多肽以及与RNA结合蛋白(RNA binding protein，RBP)相互作用等。近年来，circRNA因其自身特殊的结构以及在基因表达中发挥的重要调控作用，成为了畜禽遗传育种工作中的关注热点。羊作为中国饲养历史悠久的重要畜种，品种繁多且分布于全国各地，是人们日常生活中最常见的家畜之一。circRNA在羊的绒(毛)、肉质、泌乳、繁殖等性状中发挥着调控作用，且circRNA大多通过作为miRNA的分子海绵调节相关基因的表达，从而影响羊的各个性状。作者综述了circRNA的来源、发展、合成机制、生物功能及其在羊重要经济性状方面的最新应用，旨在为深入探究circRNA在羊重要性状中的分子调控机制提供科学参考。

关键词: 环状RNA; 羊; 经济性状

Abstract: Circular RNA (circRNA) is a new type of RNA molecule,which is formed from precursor mRNA by reverse splicing to form a covalently closed ring structure,and the lack of a cap structure and PolyA tail makes it stable and not easily degraded by nucleic acid exonucleases.With the rapid development of high-throughput sequencing and bioinformatics technology,many important regulatory function of circRNA in plant and animal life activity and disease occurrence have been explained,such as competitive binding of microRNA (miRNA),regulation of gene transcription,encoding of polypeptides,interactions with RNA binding protein (RBP),etc.In recent years,circRNA has become a hotspot in livestock and poultry genetic breeding because of their special structure and important regulatory role in gene expression.As an important livestock species with a long history of breeding in China,sheep not only have many varieties,but also are distributed all over the country,and are one of the most common livestock in people’s daily life.circRNA plays a regulatory role in various traits of sheep,such as fleece (wool),meat quality,lactation and reproduction,and circRNA mostly regulates the expression of related genes by acting as molecular sponges of miRNA,thus affecting various traits of sheep.Therefore,the authors summarize the origin,development,synthesis mechanism,biological function of circRNA and their recent applied research progress in important economic traits of sheep,so as to provide a scientific reference for in-depth investigation of the molecular regulatory mechanisms of circRNA in important traits of sheep.

Key words: circRNA; sheep; economic traits

中图分类号:

S813.3

牛舒冉, 潘剑锋, 戎友俊, 敖晓芳, 王一涵, 尚方正, 王瑞军, 张燕军. 环状RNA在羊重要经济性状中的应用研究[J]. 中国畜牧兽医, 2025, 52(6): 2468-2481.

NIU Shuran, PAN Jianfeng, RONG Youjun, AO Xiaofang, WANG Yihan, SHANG Fangzheng, WANG Ruijun, ZHANG Yanjun. Advances on the Application of Circular RNA in Important Economic Traits in Sheep[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(6): 2468-2481.

参考文献

[1] XIAO M,AI Y,WILUSZ E J.Biogenesis and functions of circular RNAs come into focus[J].Trends in Cell Biology,2020,30(3):226-240.
[2] CHEN L L,YANG L.Regulation of circRNA biogenesis[J].RNA Biology,2015,12(4):381-388.
[3] SEBASTIN M,MARVIN J,ANTIGOI E,et al.Circular RNAs are a large class of animal RNAs with regulatory potency[J].Nature,2013,495(7441):333-338.
[4] CHEN L,DUMELIE J G,LI X,et al.Global regulation of mRNA translation and stability in the early drosophila embryo by the Smaug RNA-binding protein[J].Genome Biology,2014,15(1):R4.
[5] CHEN C Y,SARNOW P.Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs[J].Science,1995,268(5209):415-417.
[6] LEI M,ZHENG G,NING Q,et al.Translation and functional roles of circular RNAs in human cancer[J].Molecular Cancer,2020,19(1):30.
[7] 刘瑶.我国羊肉产业现状及未来发展趋势[J].中国饲料,2019,17:112-117.LIU Y.Current situation and future development trend of sheep meat industry in China[J].China Feed,2019,17:112-117.(in Chinese)
[8] LIU Y,CHEN Q,BAO J,et al.Genome-wide analysis of circular RNAs reveals circCHRNG regulates sheep myoblast proliferation via miR-133/SRF and MEF2A axis[J].International Journal of Molecular Sciences,2022,23(24):16065.
[9] ZHU C,JIANG Y,ZHU J,et al.circRNA8220 sponges miR-8516 to regulate cell viability and milk synthesis via Ras/MEK/ERK and PI3K/Akt/mTOR pathways in goat mammary epithelial cells[J].Animals,2020,10(8):1347.
[10] QIAN L,VU M N,CARTER M,et al.A spliced intron accumulates as a lariat in the nucleus of T cells[J].Nucleic Acids Research,1992,20(20):5345-5350.
[11] 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 of the United States of America,1976,73(11):3852-3856.
[12] LIU J,LI D,LUO H,et al.Circular RNAs:The star molecules in cancer[J].Molecular Aspects of Medicine,2019,70：141-152.
[13] HARLAND R,MISHER L.Stability of RNA in developing xenopus embryos and identification of a destabilizing sequence in TFIIA messenger RNA[J].Development,1988,102(4):837-852.
[14] JANINA B,PATRIK B,YANNIC N,et al.What goes around comes around:Artificial circular RNAs bypass cellular antiviral responses[J].Molecular Therapy-Nucleic Acids,2022,28(14):623-635.
[15] SALZMAN J,CHEN R E,OLSEN M N,et al.Cell-type specific features of circular RNA expression[J].PLoS Genetics,2013,9(9):e1003777.
[16] 张弓,王通,何庆瑜.怎样发现未知蛋白质——翻译组测序[J].中国科学:生命科学,2014,44(2):218-220.ZHANG G,WANG T,HE Q Y.How to discover unknown proteins—Translational group sequencing[J].Science China:Life Sciences,2014,44(2):218-220.(in Chinese)
[17] CONN S J,PILLMAN K A,TOUBIA J,et al.The RNA binding protein quaking regulates formation of circRNAs[J].Cell,2015,160(6):1125-1134.
[18] DANIEL C,BEHM M,ÖHMAN M.The role of Alu elements in the cis-regulation of RNA processing[J].Cellular and Molecular Life Sciences,2015,72(21):4063-4076.
[19] LIU Z,HAN J,LV H,et al.Computational identification of circular RNAs based on conformational and thermodynamic properties in the flanking introns[J].Computational Biology and Chemistry,2016,61:221-225.
[20] ZHANG Y,XUE W,LI X,et al.The biogenesis of nascent circular RNAs[J].Cell Reports,2016,15(3):611-624.
[21] YANG Y,FAN X,MAO M,et al.Extensive translation of circular RNAs driven by N6-methyladenosine[J].Cell Research,2017,27(5):626-641.
[22] PAMUDURTI N R,BARTOK O,JENS M,et al.Translation of circRNAs[J].Molecular Cell,2017,66(1):9-21.e7.
[23] WESSELHOEFT R A,KOWALSKI P S,ANDERSON D G.Engineering circular RNA for potent and stable translation in eukaryotic cells[J].Nature Communications,2018,9(1):2629.
[24] ALTESHA M,NI T,KHAN A,et al.Circular RNA in cardiovascular disease[J].Journal of Cellular Physiology,2019,234(5):5588-5600.
[25] CHEN X,YANG T,WANG W,et al.Circular RNAs in immune responses and immune diseases[J].Theranostics,2019,9(2):588-607.
[26] QU L,YI Z,SHEN Y,et al.Circular RNA vaccines against SARS-CoV-2 and emerging variants[J].Cell,2022,185(10):1728-1744.e16.
[27] ZHANG X O,DONG R,ZHANG Y,et al.Diverse alternative back-splicing and alternative splicing landscape of circular RNAs[J].Genome Research,2016,26(9):1277-1287.
[28] JECK W R,SHARPLESS N E.Detecting and characterizing circular RNAs[J].Nature Biotechnology,2014,32(5):453-461.
[29] SALZMAN J,GAWAD C,WANG P L,et al.Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types[J].PLoS One,2012,7(2):e30733.
[30] KRISTENSEN L S,ANDERSEN M S,STAGSTED L V W,et al.The biogenesis,biology and characterization of circular RNAs[J].Nature Reviews Genetics,2019,20(11):675-691.
[31] PETAR G,PANAGIOTIS P,NIKOLAUS R.CircBase:A database for circular RNAs[J].RNA,2014,20(11):1666-1670.
[32] ZHANG Y,ZHANG X O,CHEN T,et al.Circular intronic long noncoding RNAs[J].Molecular Cell,2013,51(6):792-806.
[33] CHEN N,ZHAO G,YAN X,et al.A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1[J].Genome Biology,2018,19(1):218.
[34] 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.
[35] GENG X,JIA Y,ZHANG Y,et al.Circular RNA:Biogenesis,degradation,functions and potential roles in mediating resistance to anticarcinogens[J].Epigenomics,2020,12(3):267-283.
[36] BARRETT S P,WANG P L,SALZMAN J.Circular RNA biogenesis can proceed through an exon-containing lariat precursor[J].eLife,2015,4:e07540.
[37] HUANG C,LIANG D,TATOMER D C,et al.A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs[J].Genes & Development,2018,32(9-10):639-644.
[38] CHEN I,CHEN C Y,CHUANG T J.Biogenesis,identification,and function of exonic circular RNAs[J].Wiley Interdisciplinary Reviews.RNA,2015,6(5):563-579.
[39] QUAN G,LI J.Circular RNAs:Biogenesis,expression and their potential roles in reproduction[J].Journal of Ovarian Research,2018,11(1):9.
[40] VO J N,CIESLIK M,ZHANG Y,et al.The landscape of circular RNA in cancer[J].Cell,2019,176(4):869-881.e13.
[41] GUARNERIO J,BEZZI M,JEONG J C,et al.Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations[J].Cell,2016,165(2):289-302.
[42] LIU X,WANG X,LI J,et al.Identification of mecciRNAs and their roles in the mitochondrial entry of proteins[J].Science China.Life Sciences,2020,63(10):1429-1449.
[43] LIANG D,WILUSZ J E.Short intronic repeat sequences facilitate circular RNA production[J].Genes & Development,2014,28(20):2233-2247.
[44] ZHANG X O,WANG H B,ZHANG Y,et al.Complementary sequence-mediated exon circularization[J].Cell,2014,159(1):134-147.
[45] HOLDT L M,KOHLMAIER A,TEUPSER D.Molecular roles and function of circular RNAs in eukaryotic cells[J].Cellular and Molecular Life Sciences,2018,75(6):1071-1098.
[46] LI J,SUN D,PU W,et al.Circular RNAs in cancer:Biogenesis,function,and clinical significance[J].Trends in Cancer,2020,6(4):319-336.
[47] DE KONING A P J,GU W,CASTOE T A,et al.Repetitive elements may comprise over two-thirds of the human genome[J].PLoS Genetics,2011,7(12):e1002384.
[48] YOSHIMOTO R,RAHIMI K,HANSEN T B,et al.Biosynthesis of circular RNA ciRS-7/CDR1as is mediated by mammalian-wide interspersed repeats[J].iScience,2020,23(7):101345.
[49] IVANOV A,MEMCZAK S,WYLER E,et al.Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals[J].Cell Reports,2015,10(2):170-177.
[50] DONG W,DAI Z H,LIU F C,et al.The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA2 production[J].EBio Medicine,2019,45:155-167.
[51] ZHAO W,CUI Y,LIU L,et al.Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop[J].Cell Death and Differentiation,2020,27(3):919-933.
[52] ASHWAL-FLUSS R,MEYER M,PAMUDURTI N R,et al.CircRNA biogenesis competes with pre-mRNA splicing[J].Molecular Cell,2014,56(1):55-66.
[53] LI X,LIU C X,XUE W,et al.Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection[J].Molecular Cell,2017,67(2):214-227.e7.
[54] AKTAŞ T,AVŞAR ILIK I,MATICZKA D,et al.DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome[J].Nature,2017,544(7648):115-119.
[55] RYBAK-WOLF A,STOTTMEISTER C,GLAŽAR P,et al.Circular RNAs in the mammalian brain are highly abundant,conserved,and dynamically expressed[J].Molecular Cell,2015,58(5):870-885.
[56] ERRICHELLI L,DINI MODIGLIANI S,LANEVE P,et al.FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons[J].Nature Communications,2017,8:14741.
[57] HOUSELEY J,TOLLERVEY D.The many pathways of RNA degradation[J].Cell,2009,136(4):763-776.
[58] REN L,JIANG Q,MO L,et al.Mechanisms of circular RNA degradation[J].Communications Biology,2022,5(1):1355.
[59] LI X,ZHANG J L,LEI Y N,et al.Linking circular intronic RNA degradation and function in transcription by RNase H1[J].Science China.Life Sciences,2021,64(11):1795-1809.
[60] LIU C X,LI X,NAN F,et al.Structure and degradation of circular RNAs regulate PKR activation in innate immunity[J].Cell,2019,177(4):865-880.e21.
[61] HANSEN T B,WIKLUND E D,BRAMSEN J B,et al.miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA[J].The EMBO Journal,2011,30(21):4414-4422.
[62] PAN Z,LI G F,SUN M L,et al.microRNA-1224 splicing circularRNA-Filip11 in an Ago2-dependent manner regulates chronic inflammatory pain via targeting Ubr5[J].The Journal of Neuroscience,2019,39(11):2125-2143.
[63] PARK O H,HA H,LEE Y,et al.Endoribonucleolytic cleavage of m⁶A-containing RNAs by RNase P/MRP complex[J].Molecular Cell,2019,74(3):494-507.e8.
[64] FISCHER J W,BUSA V F,SHAO Y,et al.Structure-mediated RNA decay by UPF1 and G3BP1[J].Molecular Cell,2020,78(1):70-84.e6.
[65] LASDA E,PARKER R.Circular RNAs co-precipitate with extracellular vesicles:A possible mechanism for circRNA clearance[J].PLoS One,2016,11(2):e0148407.
[66] BARTEL D P.microRNAs:Target recognition and regulatory functions[J].Cell,2009,136(2):215-233.
[67] LU T X,ROTHENBERG M E.microRNA[J].The Journal of Allergy and Clinical Immunology,2018,141(4):1202-1207.
[68] PANDA A C.Circular RNAs act as miRNA sponges[J].Advances in Experimental Medicine and Biology,2018,1087:67-79.
[69] THOMSON D W,DINGER M E.Endogenous microRNA sponges:Evidence and controversy[J].Nature Reviews.Genetics,2016,17(5):272-283.
[70] LIU J T,YAO Q P,CHEN Y,et al.Arterial cyclic stretch regulates Lamtor1 and promotes neointimal hyperplasia via circSlc8a1/miR-20a-5p axis in vein grafts[J].Theranostics,2022,12(11):4851-4865.
[71] LU Q,LIU T,FENG H,et al.Circular RNA circSlc8a1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating pten[J].Molecular Cancer,2019,18(1):111.
[72] LIM T B,ALIWARGA E,LUU T D A,et al.Targeting the highly abundant circular RNA circSlc8a1 in cardiomyocytes attenuates pressure overload induced hypertrophy[J].Cardiovascular Research,2019,115(14):1998-2007.
[73] ZANG J,LU D,XU A.The interaction of circRNAs and RNA binding proteins:An important part of circRNA maintenance and function[J].Journal of Neuroscience Research,2020,98(1):87-97.
[74] ABDELMOHSEN K,PANDA A C,MUNK R,et al.Identification of hur target circular RNAs uncovers suppression of PABPN1 translation by circPABPN1[J].RNA Biology,2017,14(3):361-369.
[75] WU N,YUAN Z,DU K Y,et al.Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery[J].Cell Death and Differentiation,2019,26(12):2758-2773.
[76] ZHANG M,HUANG N,YANG X,et al.A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis[J].Oncogene,2018,37(13):1805-1814.
[77] 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.
[78] SHANG F,WANG Y,MA R,et al.Expression profiling and functional analysis of circular RNAs in Inner Mongolian cashmere goat hair follicles[J].Frontiers in Genetics,2021,12:678825.
[79] SHANG F,MA R,RONG Y,et al.Construction and functional analysis of ceRNA regulatory network related to the development of secondary hair follicles in Inner Mongolia cashmere goats[J].Frontiers in Veterinary Science,2022,9:959952.
[80] KIRGIAFINI D,KYRGIAFINI M A,GOURNARIS T,et al.Understanding circular RNAs in health,welfare,and productive traits of cattle,goats,and sheep[J].Animals,2024,14(5):733.
[81] GAO Y,SONG W,HAO F,et al.Effect of fibroblast growth factor 10 and an interacting non-coding RNA on secondary hair follicle dermal papilla cells in cashmere goats’ follicle development assessed by whole-transcriptome sequencing technology[J].Animals,2023,13(13):2234.
[82] GONG G,FAN Y,ZHANG Y,et al.The regulation mechanism of different hair types in Inner Mongolia cashmere goat based on PI3K-Akt pathway and FGF21[J].Journal of Animal Science,2022,100(11):skac292.
[83] ZHENG Y,HUI T,YUE C,et al.Comprehensive analysis of circRNAs from cashmere goat skin by next generation RNA sequencing (RNA-Seq)[J].Scientific Reports,2020,10(1):516.
[84] HUI T,ZHENG Y,YUE C,et al.Screening of cashmere fineness-related genes and their ceRNA network construction in cashmere goats[J].Scientific Reports,2021,11(1):21977.
[85] HU L,WANG J,LUO Y,et al.Identification and characterization of circular RNAs (circRNAs) using RNA-Seq in two breeds of cashmere goats[J].Genes,2023,14(2):331.
[86] WANG J,WU X,KANG Y,et al.Integrative analysis of circRNAs from Yangtze river Delta White goat neck skin tissue by high-throughput sequencing (circRNA-Seq)[J].Animal Genetics,2022,53(3):405-415.
[87] YIN R,YIN R,BAI M,et al.N6-methyladenosine modification (m⁶A) of circRNA-ZNF638 contributes to the induced activation of SHF stem cells through miR-361-5p/Wnt5a axis in cashmere goats[J].Animal Bioscience,2023,36(4):555-569.
[88] ZHANG Q,FAN Y,BAI M,et al.circERCC6 positively regulates the induced activation of SHF stem cells in cashmere goats via the miR-412-3p/BNC2 axis in an m⁶A-dependent manner[J].Animals,2024,14(2):187.
[89] HUI T,ZHU Y,SHEN J,et al.Identification and molecular analysis of m⁶A-circRNAs from cashmere goat reveal their integrated regulatory network and putative functions in secondary hair follicle during anagen stage[J].Animals,2022,12(6):694.
[90] LV X,CHEN W,SUN W,et al.Expression profile analysis to identify circular RNA expression signatures in hair follicle of Hu sheep lamb skin[J].Genomics,2020,112(6):4454-4462.
[91] ZHAO R,LIU N,HAN F,et al.Identification and characterization of circRNAs in the skin during wool follicle development in Aohan fine wool sheep[J].BMC Genomics,2020,21(1):187.
[92] ZHAO B,LUO H,HE J,et al.Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep[J].BMC Biology,2021,19(1):197.
[93] ZHANG X,LIU C,KONG Y,et al.Effects of intramuscular fat on meat quality and its regulation mechanism in Tan sheep[J].Frontiers in Nutrition,2022,9:908355.
[94] CAO Y,YOU S,YAO Y,et al.Expression profiles of circular RNAs in sheep skeletal muscle[J].Asian-Australasian Journal of Animal Sciences,2018,31(10):1550-1557.
[95] BAO G,ZHAO F,WANG J,et al.Characterization of the circRNA-miRNA-mRNA network to reveal the potential functional ceRNAs associated with dynamic changes in the meat quality of the longissimus thoracis muscle in Tibetan sheep at different growth stages[J].Frontiers in Veterinary Science,2022,9:803758.
[96] ZHAO L,ZHOU L,HAO X,et al.Identification and characterization of circular RNAs in association with the deposition of intramuscular fat in Aohan fine-wool sheep[J].Frontiers in Genetics,2021,12:759747.
[97] CUI R,KANG X,LIU Y,et al.Integrated analysis of the whole transcriptome of skeletal muscle reveals the ceRNA regulatory network related to the formation of muscle fibers in Tan sheep[J].Frontiers in Genetics,2022,13:991606.
[98] HAO Z,ZHOU H,HICKFORD J G H,et al.Identification and characterization of circular RNA in lactating mammary glands from two breeds of sheep with different milk production profiles using RNA-Seq[J].Genomics,2020,112(3):2186-2193.
[99] WU X,ZHEN H,LIU Y,et al.Tissue-specific expression of circ_015343 and its inhibitory effect on mammary epithelial cells in sheep[J].Frontiers in Veterinary Science,2022,9:919162.
[100] WANG J,ZHOU H,HICKFORD J G H,et al.Identification and characterization of circular RNAs in mammary gland tissue from sheep at peak lactation and during the nonlactating period[J].Journal of Dairy Science,2021,104(2):2396-2409.
[101] CHEN W,GU X,LV X,et al.Non-coding transcriptomic profiles in the sheep mammary gland during different lactation periods[J].Frontiers in Veterinary Science,2022,9:983562.
[102] CHEN Z,WANG Y,WANG K,et al.circRNA-02191 regulating unsaturated fatty acid synthesis by adsorbing miR-145 to enhance CD36 expression in bovine mammary gland[J].International Journal of Biological Macromolecules,2023,244:125306.
[103] CHEN Z,LU Q,ZHANG X,et al.circ007071 inhibits unsaturated fatty acid synthesis by interacting with miR-103-5p to enhance PPARγ expression in the dairy goat mammary gland[J].Journal of Agricultural and Food Chemistry,2022,70(42):13719-13729.
[104] JIAO P,ZHANG M,WANG Z,et al.circ003429 regulates unsaturated fatty acid synthesis in the dairy goat mammary gland by interacting with miR-199a-3p,targeting the YAP1 gene[J].International Journal of Molecular Sciences,2022,23(7):4068.
[105] XUAN R,WANG J,LI Q,et al.Identification and characterization of circRNAs in non-lactating dairy goat mammary glands reveal their regulatory role in mammary cell involution and remodeling[J].Biomolecules,2023,13(5):860.