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PMID:20603131

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Citation

Cai, L, Fritz, D, Stefanovic, L and Stefanovic, B (2010) Nonmuscle myosin-dependent synthesis of type I collagen. J. Mol. Biol. 401:564-78

Abstract

Type I collagen, synthesized in all tissues as the heterotrimer of two alpha1(I) polypeptides and one alpha2(I) polypeptide, is the most abundant protein in the human body. Here we show that intact nonmuscle myosin filaments are required for the synthesis of heterotrimeric type I collagen. Conserved 5' stem-loop in collagen alpha1(I) and alpha2(I) mRNAs binds the RNA-binding protein LARP6. LARP6 interacts with nonmuscle myosin through its C-terminal domain and associates collagen mRNAs with the filaments. Dissociation of nonmuscle myosin filaments results in secretion of collagen alpha1(I) homotrimer, diminished intracellular colocalization of collagen alpha1(I) and alpha2(I) polypeptides (required for folding of the heterotrimer), and their increased intracellular degradation. Inhibition of the motor function of myosin has similar collagen-specific effects, while disruption of actin filaments has a general effect on protein secretion. Nonmuscle myosin copurifies with polysomes, and there is a subset of polysomes involved in myosin-dependent translation of collagen mRNAs. These results indicate that association of collagen mRNAs with nonmuscle myosin filaments is necessary to coordinately synthesize collagen alpha1(I) and alpha2(I) polypeptides. We postulate that LARP6/myosin-dependent mechanism regulates the synthesis of heterotrimeric type I collagen by coordinating the translation of collagen mRNAs.

Links

PubMed PMC3674529 Online version:10.1016/j.jmb.2010.06.057

Keywords

Animals; Cells, Cultured; Collagen Type I/biosynthesis; Humans; Mice; Mice, Knockout; Myosins/metabolism; Polyribosomes/metabolism; RNA, Messenger/metabolism; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism

Significance

Annotations

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

HUMAN:CO1A1

located_in

GO:0005615: extracellular space

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CO2A1

located_in

GO:0005615: extracellular space

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:VIME

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BRS8

F

Seeded From UniProt

complete

HUMAN:MYH9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BRS8

F

Seeded From UniProt

complete

HUMAN:MYH10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BRS8

F

Seeded From UniProt

complete

HUMAN:MYH10

located_in

GO:0005829: cytosol

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P08670

F

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0035613: RNA stem-loop binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0017022: myosin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35579

F

Seeded From UniProt

complete

HUMAN:LARP6

enables

GO:0017022: myosin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35580

F

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:0048027: mRNA 5'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:VIME

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Q4LE45

enables

GO:0035613: RNA stem-loop binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q4LE45

part_of

GO:0005844: polysome

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Q4LE45

part_of

GO:0005829: cytosol

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Q4LE45

enables

GO:0048027: mRNA 5'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q4LE45

involved_in

GO:0050714: positive regulation of protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYH10

enables

GO:0035613: RNA stem-loop binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MYH10

part_of

GO:0005844: polysome

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH10

part_of

GO:0005829: cytosol

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH10

enables

GO:0048027: mRNA 5'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MYH10

involved_in

GO:0050714: positive regulation of protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CO2A1

part_of

GO:0005615: extracellular space

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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