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PMID:22190748

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Citation

Manojlovic, Z and Stefanovic, B (2012) A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs. RNA 18:321-34

Abstract

Type I collagen is composed of two α1(I) polypeptides and one α2(I) polypeptide and is the most abundant protein in the human body. Expression of type I collagen is primarily controlled at the level of mRNA stability and translation. Coordinated translation of α(I) and α2(I) mRNAs is necessary for efficient folding of the corresponding peptides into the collagen heterotrimer. In the 5' untranslated region (5' UTR), collagen mRNAs have a unique 5' stem-loop structure (5' SL). La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6. In vivo, collagen mRNAs immunoprecipitate with RHA in an LARP6-dependent manner. Knockdown of RHA prevents formation of polysomes on collagen mRNAs and dramatically reduces synthesis of collagen protein, without affecting the level of the mRNAs. A reporter mRNA with collagen 5' SL is translated three times more efficiently in the presence of RHA than the same reporter without the 5' SL, indicating that the 5' SL is the cis-acting element conferring the regulation. During activation of quiescent cells into collagen-producing cells, expression of RHA is highly up-regulated. We postulate that RHA is recruited to the 5' UTR of collagen mRNAs by LARP6 to facilitate their translation. Thus, RHA has been discovered as a critical factor for synthesis of the most abundant protein in the human body.

Links

PubMed PMC3264918 Online version:10.1261/rna.030288.111

Keywords

5' Untranslated Regions; Autoantigens/metabolism; Cells, Cultured; Collagen Type I/biosynthesis; Collagen Type I/genetics; Collagen Type I/metabolism; DEAD-box RNA Helicases/metabolism; Fibroblasts/metabolism; HEK293 Cells; Hepatic Stellate Cells/metabolism; Humans; Neoplasm Proteins/metabolism; Polyribosomes/metabolism; Protein Folding; Protein Interaction Domains and Motifs/genetics; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins/biosynthesis; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Ribonucleoproteins/metabolism; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DHX9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BRS8

F

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q08211

F

Seeded From UniProt

complete

HUMAN:LARP6

part_of

GO:1990904: ribonucleoprotein complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LARP6

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:1990825: sequence-specific mRNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0048027: mRNA 5'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:LARP6

involved_in

GO:1902416: positive regulation of mRNA binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DHX9

part_of

GO:1990904: ribonucleoprotein complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DHX9

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DHX9

involved_in

GO:2000767: positive regulation of cytoplasmic translation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DHX9

involved_in

GO:1905698: positive regulation of polysome binding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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