title: Antagonistic roles of Nibbler and Hen1 in modulating piRNA 3' ends in Drosophila.
abstract: In eukaryotes, aberrant expression of transposable elements (TEs) is detrimental to the host genome. Piwi-interacting RNAs (piRNAs) of ∼23 to 30 nucleotides bound to PIWI clade Argonaute proteins silence transposons in a manner that is strictly dependent on their sequence complementarity. Hence, a key goal in understanding piRNA pathways is to determine mechanisms that modulate piRNA sequences. Here, we identify a protein-protein interaction between the 3'-to-5' exoribonuclease Nibbler (Nbr) and Piwi that links Nbr activity with piRNA pathways. We show that there is a delicate balance in the interplay between Nbr and Hen1, a methyltransferase involved in 2'-O-methylation at the 3' terminal nucleotides of piRNAs, thus connecting two genes with opposing activities in the biogenesis of piRNA 3' ends. With age, piRNAs become shorter and fewer in number, which is coupled with the derepression of select TEs. We demonstrate that activities of Nbr and Hen1 inherently contribute to TE silencing and age-dependent profiles of piRNAs. We propose that antagonistic roles of Nbr and Hen1 define a mechanism to modulate piRNA 3' ends.
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Kongyan
authors.initials: K
authors.lastname: Niu
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Zilkha Neurogenetic Institute, University of South California, Los Angeles, CA 90033, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China zyy@sioc.ac.cn liunan@sioc.ac.cn.
authors.forename: Yaoyang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China zyy@sioc.ac.cn liunan@sioc.ac.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000235:genetics; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004251:DNA Transposable Elements / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D049750:Genome, Insect; D005854:Germ Cells / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C521948:Hen1 protein, Drosophila; D008780:Methyltransferases; D005095:Exoribonucleases; C570892:Nbr protein, Drosophila
keywords: 2′-O-methylation; 3′ terminal trimming; Drosophila; Hen1; Nbr; Small RNA sequencing; Transposon; piRNA