title: Interaction between microRNAs and actin-associated protein Arpc5 regulates translational suppression during male germ cell differentiation.
abstract: Decoupling of transcription and translation during postmeiotic germ cell differentiation is critical for successful spermatogenesis. Here we establish that the interaction between microRNAs and actin-associated protein Arpc5 sets the stage for an elaborate translational control mechanism by facilitating the sequestration of germ cell mRNAs into translationally inert ribonucleoprotein particles until they are later translated. Our studies reveal that loss of microRNA-dependent regulation of Arpc5, which controls the distribution of germ cell mRNAs between translationally active and inactive pools, results in abnormal round spermatid differentiation and impaired fertility. Interestingly, Arpc5 functions as a broadly acting translational suppressor, as it inhibits translation initiation by blocking 80S formation and facilitates the transport of mRNAs to chromatoid/P bodies. These findings identify a unique role for actin-associated proteins in translational regulation, and suggest that mRNA-specific and general translational control mechanisms work in tandem to regulate critical germ cell differentiation events and diverse somatic cell functions.
authors.affiliation: Greehey Children's Cancer Research Institute and Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Yao-Fu
authors.initials: YF
authors.lastname: Chang
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lee-Chang
authors.forename: J Saadi
authors.initials: JS
authors.lastname: Imam
authors.forename: Kalyan Chakravarthy
authors.initials: KC
authors.lastname: Buddavarapu
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Subaran
authors.forename: Amiya P
authors.initials: AP
authors.lastname: Sinha-Hikim
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Manjeet K
authors.initials: MK
authors.lastname: Rao
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006238:Haploidy; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011479:Protamines / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction; D043244:Ribonuclease III / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013077:Sperm Head / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology*; D013737:Testis / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure
chemical_list: D051376:Actin-Related Protein 2-3 Complex; C572494:Arpc5 protein, mouse; D002843:Chromatin; D035683:MicroRNAs; D011479:Protamines; D012333:RNA, Messenger; D043244:Ribonuclease III