Authors: Chong Qiao, Jing Ma, Jie Xu, Mingyi Xie, Wei Ma and Yingqun Huang

Chong Qiao

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Department of Obstetrics and Gynecology; Shengjing Hospital; China Medial University; Shengyang, Liaoning, China

Jing Ma

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Obstetrics and Gynecology Department; Third Xiangya Hospital of Central South University; Changsha, Hunan, China

Jie Xu

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA

Mingyi Xie

Department of Molecular Biophysics and Biochemistry; Boyer Center for Molecular Medicine; Yale University School of Medicine; New Haven, CT USA

Wei Ma

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Clinical Department, School of Medicine; Northwest University for Nationalities; Lanzhou, Gansu, China

Yingqun Huang

Corresponding author: yingqun.huang@yale.edu
Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA

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.

Received: July 11, 2012; Accepted: August 16, 2012; Published Online: August 30, 2012

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