Systematic characterization of small RNAs associated with C.elegans Argonautes  

作　　者：Lei Liu Xiaolin Wang Wenfang Zhao Qiqi Li Jingxin Li He Chen Ge Shan 

机构地区：[1]Department of Laboratory Medicine,The First Affiliated Hospital of USTC,the CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Science and Medicine,University of Science and Technology of China,Hefei,230027,China [2]Information Materials and Intelligent Sensing Laboratory of Anhui Province,Anhui University,Hefei,230601,China [3]Department of Pulmonary and Critical Care Medicine,Regional Medical Center for National Institute of Respiratory Diseases,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou,310016,China

出　　处：《Science China(Life Sciences)》2023年第6期1303-1322,共20页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China (2019YFA0802600);the National Natural Science Foundation of China (31930019,31900442,32200431);the Strategic Priority Research Program“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences (XDB39010400);the China Postdoctoral Science Foundation (2022M713053)。

摘　　要：Argonaute proteins generally play regulatory roles by forming complexes with the corresponding small RNAs(s RNAs).An expanded Argonaute family with 20 potentially functional members has been identified in Caenorhabditis elegans.Canonical s RNAs in C.elegans are mi RNAs,small interfering RNAs including 22G-RNAs and 26G-RNAs,and 21U-RNAs,which are C.elegans pi RNAs.Previous studies have only covered some of these Argonautes for their s RNA partners,and thus,a systematic study is needed to reveal the comprehensive regulatory networks formed by C.elegans Argonautes and their associated s RNAs.We obtained in situ knockin(KI)strains of all C.elegans Argonautes with fusion tags by CRISPR/Cas9 technology.RNA immunoprecipitation against these endogenously expressed Argonautes and high-throughput sequencing acquired the s RNA profiles of individual Argonautes.The s RNA partners for each Argonaute were then analyzed.We found that there were 10Argonautes enriched mi RNAs,17 Argonautes bound to 22G-RNAs,8 Argonautes bound to 26G-RNAs,and 1 Argonaute PRG-1bound to pi RNAs.Uridylated 22G-RNAs were bound by four Argonautes HRDE-1,WAGO-4,CSR-1,and PPW-2.We found that all four Argonautes played a role in transgenerational epigenetic inheritance.Regulatory roles of the corresponding Argonaute-s RNA complex in managing levels of long transcripts and interspecies regulation were also demonstrated.In this study,we portrayed the s RNAs bound to each functional Argonaute in C.elegans.Bioinformatics analyses together with experimental investigations provided perceptions in the overall view of the regulatory network formed by C.elegans Argonautes and s RNAs.The s RNA profiles bound to individual Argonautes reported here will be valuable resources for further studies.

关 键 词：ARGONAUTE miRNA 22G-RNAs 26G-RNAs PIRNA uridylation transgenerational inheritance INTERSPECIES 

分 类 号：Q75[生物学—分子生物学]