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“ Alu” strious effects on human RNA metabolism: post‐transcriptional gene regulation by intermolecular and intramolecular Alu element base‐pairing (102.1)
Author(s) -
Maquat Lynne
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.102.1
Subject(s) - alu element , untranslated region , three prime untranslated region , biology , five prime untranslated region , genetics , rna binding protein , base pair , rna , translation (biology) , messenger rna , gene , microbiology and biotechnology , au rich element , human genome , genome
Staufen1‐mediated mRNA decay (SMD), which occurs when translation terminates sufficiently upstream of a STAU1‐binding site (SBS), is important for myogenesis, adipogenesis and many other developmental and homeostatic pathways 1 . An SBS can be created by intra molecular base‐pairing within an mRNA 3'‐untranslated region (3'UTR) or by inter molecular base‐pairing between an mRNA 3'UTR Alu element and the Alu element within a long non‐coding RNA (lncRNA), which we call a ½‐sbsRNA. Alu elements are a type of small interspersed repetitive element (SINE) 2 restricted to humans and other primates. Notably, SMD in rodents is triggered by intermolecular base‐pairing between B or identifier (ID) SINEs 3 . Roles of STAU1 dimerization 4 and the STAU1 paralog STAU2 5 in SMD will be discussed as will a new mechanism in which mRNAs autoelicit SMD via direct mRNA−mRNA base‐pairing between their 3'UTR Alu elements. We show that this mechanism is important for cell migration and invasion 6 . This unexpected function for mRNAs, together with our discovery of how STAU1 binding to inverted repeated 3'UTR Alu elements (IR Alu s) competes with nuclear retention mediated by p54 nrb binding to 3'UTR IR Alu s and also the repression of cytoplasmic translation mediated by protein kinase R (PKR) binding to 3'UTR IR Alu s 7 , adds unexpected complexity to post‐transcriptional regulatory mechanisms. 1 Park, Maquat (2013) WIRES 4:423‐5. 2 Gong, Maquat (2011) Nature 470: 284‐8. 3 Wang et al. (2013) Genes Dev , 27: 793‐804. 4 Gleghorn et al. (2013) NSMB , 20:515‐24. 5 Park et al. (2013) PNAS , 110: 405‐12. 6 Gong et al. (2013) NSMB, in press. 7 Elbarbary (2013) Genes Dev. 27:1495‐1510.