You are here

Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.

Title: Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.
2 views
0 downloads
Name(s): Wang, Hao, author
Stefanovic, Branko, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2014-10-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Type I collagen is extracellular matrix protein composed of two α1(I) and one α2(I) polypeptides that fold into triple helix. Collagen polypeptides are translated in coordination to synchronize the rate of triple helix folding to the rate of posttranslational modifications of individual polypeptides. This is especially important in conditions of high collagen production, like fibrosis. It has been assumed that collagen mRNAs are targeted to the membrane of the endoplasmic reticulum (ER) after translation of the signal peptide and by signal peptide recognition particle (SRP). Here we show that collagen mRNAs associate with the ER membrane even when translation is inhibited. Knock down of LARP6, an RNA binding protein which binds 5' stem-loop of collagen mRNAs, releases a small amount of collagen mRNAs from the membrane. Depolimerization of nonmuscle myosin filaments has a similar, but stronger effect. In the absence of LARP6 or nonmuscle myosin filaments collagen polypeptides become hypermodified, are poorly secreted and accumulate in the cytosol. This indicates lack of coordination of their synthesis and retro-translocation due to hypermodifications and misfolding. Depolimerization of nonmuscle myosin does not alter the secretory pathway through ER and Golgi, suggesting that the role of nonmuscle myosin is primarily to partition collagen mRNAs to the ER membrane. We postulate that collagen mRNAs directly partition to the ER membrane prior to synthesis of the signal peptide and that LARP6 and nonmuscle myosin filaments mediate this process. This allows coordinated initiation of translation on the membrane bound collagen α1(I) and α2(I) mRNAs, a necessary step for proper synthesis of type I collagen.
Identifier: FSU_pmch_25271881 (IID), 10.1371/journal.pone.0108870 (DOI), PMC4182744 (PMCID), 25271881 (RID), 25271881 (EID), PONE-D-14-22936 (PII)
Grant Number: R01 DK059466-07A2
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182744.
Subject(s): Autoantigens/genetics
Autoantigens/metabolism
Cell Line
Collagen Type I/genetics
Collagen Type I/metabolism
Endoplasmic Reticulum/metabolism
Humans
Intracellular Membranes/metabolism
Myosins/genetics
Myosins/metabolism
RNA, Messenger/genetics
RNA, Messenger/metabolism
Ribonucleoproteins/genetics
Ribonucleoproteins/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_25271881
Owner Institution: FSU
Is Part Of: PloS one.
1932-6203
Issue: iss. 10, vol. 9

Choose the citation style.
Wang, H., & Stefanovic, B. (2014). Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane. Plos One. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_25271881