title: Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.
abstract: In mammals, small RNAs are important players in post-transcriptional gene regulation. While their roles in mRNA destabilization and translational repression are well appreciated, their involvement in endonucleolytic cleavage of target RNAs is poorly understood. Very few microRNAs are known to guide RNA cleavage. Endogenous small interfering RNAs are expected to induce target cleavage, but their target genes remain largely unknown. We report a systematic study of small RNA-mediated endonucleolytic cleavage in mouse through integrative analysis of small RNA and degradome sequencing data without imposing any bias toward known small RNAs. Hundreds of small cleavage-inducing RNAs and their cognate target genes were identified, significantly expanding the repertoire of known small RNA-guided cleavage events. Strikingly, both small RNAs and their target sites demonstrated significant overlap with retrotransposons, providing evidence for the long-standing speculation that retrotransposable elements in mRNAs are leveraged as signals for gene targeting. Furthermore, our analysis showed that the RNA cleavage pathway is also present in human cells but affecting a different repertoire of retrotransposons. These results show that small RNA-guided cleavage is more widespread than previously appreciated. Their impact on retrotransposons in non-coding regions shed light on important aspects of mammalian gene regulation.
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Cass
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Bahn
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Greer
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Lin
authors.affiliation: School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA UCLA Broad Stem Cell Research Center, Los Angeles, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Yun-Hua Esther
authors.initials: YH
authors.lastname: Hsiao
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA gxxiao@ucla.edu.
authors.forename: Xinshu
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000196:embryology / Q000201:enzymology; D053595:Embryonic Stem Cells / Q000201:enzymology; D004722:Endoribonucleases / Q000378:metabolism*; D023281:Genomics; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D059367:RNA Cleavage; D058727:RNA, Small Untranslated / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements; D013737:Testis / Q000196:embryology / Q000201:enzymology
chemical_list: D058727:RNA, Small Untranslated; D018626:Retroelements; D004722:Endoribonucleases