NDLI: Characterization of binding of LARP6 to the 5’ stem-loop of collagen mRNAs: Implications for synthesis of type I collagen

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Characterization of binding of LARP6 to the 5’ stem-loop of collagen mRNAs: Implications for synthesis of type I collagen

Content Provider	PubMed Central
Author	Stefanovic, Lela Longo, Liam Zhang, Yujie Stefanovic, Branko
Copyright Year	2014
Abstract	Type I collagen is composed of 2 polypeptides, α1(I) and α2(I), which fold into triple helix. Collagen α1(I) and α2(I) mRNAs have a conserved stem-loop structure in their 5’ UTRs, the 5’SL. LARP6 binds the 5’SL to regulate type I collagen expression. We show that 5 nucleotides within the single stranded regions of 5’SL contribute to the high affinity of LARP6 binding. Mutation of individual nucleotides abolishes the binding in gel mobility shift assay. LARP6 binding to 5’SL of collagen α2(I) mRNA is more stable than the binding to 5’SL of α1(I) mRNA, although the equilibrium binding constants are similar. The more stable binding to α2(I) mRNA may favor synthesis of the heterotrimeric type I collagen. LARP6 needs 2 domains to contact 5’SL, the La domain and the RRM. T133 in the La domain is critical for folding of the protein, while loop 3 in the RRM is critical for binding 5’SL. Loop 3 is also involved in the interaction of LARP6 and protein translocation channel SEC61. This interaction is essential for type I collagen synthesis, because LARP6 mutant which binds 5’SL but which does not interact with SEC61, suppresses collagen synthesis in a dominant negative manner. We postulate that LARP6 directly targets collagen mRNAs to the SEC61 translocons to facilitate coordinated translation of the 2 collagen mRNAs. The unique sequences of LARP6 identified in this work may have evolved to enable its role in type I collagen biosynthesis.
Related Links	http://dx.doi.org/10.1080/15476286.2014.996467
Ending Page	1401
Starting Page	1386
File Format	PDF
ISSN	15558584
e-ISSN	15558584
Journal	RNA Biology
Issue Number	11
Volume Number	11
Language	English
Publisher	Taylor & Francis
Publisher Date	2015-02-18
Access Restriction	Open
Rights Holder	Taylor & Francis
Subject Keyword	RNA Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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