title: Drosha mediates destabilization of Lin28 mRNA targets.
abstract: Lin28 plays important roles in development, stem cell maintenance, oncogenesis and metabolism. As an RNA-binding protein, it blocks the biogenesis primarily of let-7 family miRNAs and also promotes translation of a cohort of mRNAs involved in cell growth, metabolism and pluripotency, likely through recognition of distinct sequence and structural motifs within mRNAs. Here, we show that one such motif, shared by multiple Lin28-responsive elements (LREs) present in Lin28 mRNA targets also participates in a Drosha-dependent regulation and may contribute to destabilization of its cognate mRNAs. We further show that the same mutations in the LREs known to abolish Lin28 binding and stimulation of translation also abrogate Drosha-dependent mRNA destabilization, and that this effect is independent of miRNAs, uncovering a previously unsuspected coupling between Drosha-dependent destabilization and Lin28-mediated regulation. Thus, Lin28-dependent stimulation of translation of target mRNAs may, in part, serve to compensate for their intrinsic instability, thereby ensuring optimal levels of expression of genes critical for cell viability, metabolism and pluripotency.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Qiao
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Mingyi
authors.initials: M
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017930:Genes, Reporter / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: C000715187:Lin28A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III