mRNA–mRNA duplexes that auto-elicit Staufen1-mediated mRNA decay

We report a new mechanism by which human mRNAs cross-talk: an Alu element in the 3′ untranslated region (3′ UTR) of one mRNA can base-pair with a partially complementary Alu element in the 3′ UTR of a different mRNA, thereby creating a Staufen1 (STAU1)-binding site (SBS). STAU1 binding to a 3′-UTR SBS was previously shown to trigger STAU1-mediated mRNA decay (SMD) by directly recruiting the ATP-dependent RNA helicase UPF1, which is also a key factor in the mechanistically related nonsense-mediated mRNA decay (NMD) pathway. In the case of a 3′-UTR SBS created by mRNA-mRNA base-pairing, we show that SMD targets both mRNAs in the duplex, provided that both mRNAs are translated. If only one mRNA is translated, then it alone is targeted for SMD. We demonstrate the functional importance of mRNA–mRNA–triggered SMD in cell migration and invasion.

[1]  D. Weigel,et al.  ceRNAs: miRNA Target Mimic Mimics , 2011, Cell.

[2]  David H. Mathews,et al.  RNAstructure: software for RNA secondary structure prediction and analysis , 2010, BMC Bioinformatics.

[3]  Luc DesGroseillers,et al.  Mammalian Staufen1 Recruits Upf1 to Specific mRNA 3′UTRs so as to Elicit mRNA Decay , 2005, Cell.

[4]  F. Bonneau,et al.  NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity , 2008, Nature Structural &Molecular Biology.

[5]  L. Maquat,et al.  Biochemical analysis of long non-coding RNA-containing ribonucleoprotein complexes. , 2012, Methods.

[6]  Bin Tian,et al.  STAU1 binding 3' UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown. , 2013, Genes & development.

[7]  L. Maquat,et al.  Staufen‐mediated mRNA decay , 2013, Wiley interdisciplinary reviews. RNA.

[8]  T. Duchaine,et al.  Multimerization of Staufen1 in live cells. , 2010, RNA.

[9]  H. Urlaub,et al.  The cryo-EM structure of the UPF–EJC complex shows UPF1 poised toward the RNA 3′ end , 2012, Nature Structural &Molecular Biology.

[10]  L. Maquat,et al.  Staufen1 dimerizes via a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay , 2013, Nature Structural &Molecular Biology.

[11]  L. Maquat,et al.  Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin beta. , 2009, Genes & development.

[12]  [22] Psoralen cross-linking of ribosomal RNA , 1988 .

[13]  L. Maquat,et al.  lncRNAs transactivate Staufen1-mediated mRNA decay by duplexing with 3'UTRs via Alu elements , 2010, Nature.

[14]  L. Maquat,et al.  “Alu”strious long ncRNAs and their roles in shortening mRNA half-lives , 2011, Cell cycle.

[15]  R. M. Marión,et al.  A Human Sequence Homologue of Staufen Is an RNA-Binding Protein That Is Associated with Polysomes and Localizes to the Rough Endoplasmic Reticulum , 1999, Molecular and Cellular Biology.

[16]  Ferdinando Di Cunto,et al.  Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs , 2011, Cell.

[17]  L. Maquat,et al.  Control of myogenesis by rodent SINE-containing lncRNAs. , 2013, Genes & development.

[18]  P. Pandolfi,et al.  In Vivo Identification of Tumor- Suppressive PTEN ceRNAs in an Oncogenic BRAF-Induced Mouse Model of Melanoma , 2011, Cell.

[19]  L. Maquat,et al.  Staufen1 regulates diverse classes of mammalian transcripts , 2007, The EMBO journal.

[20]  L. Maquat,et al.  SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. , 2009, Genes & development.

[21]  Yoon Ki Kim,et al.  Staufen1-mediated mRNA decay functions in adipogenesis. , 2012, Molecular cell.

[22]  E. Wagner,et al.  AP-1: a double-edged sword in tumorigenesis , 2003, Nature Reviews Cancer.

[23]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[24]  K. Nishida,et al.  Mechanisms and consequences of alternative polyadenylation. , 2011, Molecules and Cells.

[25]  M. Hentze,et al.  Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation. , 2006, RNA.

[26]  D. Cacchiarelli,et al.  A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA , 2011, Cell.

[27]  M. Hentze,et al.  Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. , 2005, Molecular cell.

[28]  M. Karin,et al.  AP-1 as a regulator of cell life and death , 2002, Nature Cell Biology.

[29]  M. Wilkinson,et al.  Regulation of nonsense‐mediated mRNA decay , 2012, Wiley interdisciplinary reviews. RNA.

[30]  L. Maquat,et al.  The Pioneer Round of Translation: Features and Functions , 2010, Cell.

[31]  宮澤 悠里.  CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation , 2010 .

[32]  Xuerui Yang,et al.  An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma , 2011, Cell.

[33]  L. Maquat,et al.  Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity , 2012, Proceedings of the National Academy of Sciences.

[34]  J. Schmitz.  SINEs as driving forces in genome evolution. , 2012, Genome dynamics.