A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs

作者：Manojlovic Zarko; Stefanovic Branko^*

来源：RNA-A Publication of the RNA Society, 2012, 18(2): 321-334.

DOI：10.1261/rna.030288.111

• RNA helicase A (RHA)
• La ribonucleoprotein domain family member 6 (LARP6)
• type I collagen
• post-transcriptional control element (PCE)
• 5 %26apos
• stem-loop (5 %26apos
• SL)
• translation

Type I collagen is composed of two alpha 1(I) polypeptides and one alpha 2(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 alpha(I) and alpha 2(I) mRNAs is necessary for efficient folding of the corresponding peptides into the collagen heterotrimer. In the 5%26apos; untranslated region (5%26apos; UTR), collagen mRNAs have a unique 5%26apos; stem-loop structure (5%26apos; SL). La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5%26apos; SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5%26apos; 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%26apos; SL is translated three times more efficiently in the presence of RHA than the same reporter without the 5%26apos; SL, indicating that the 5%26apos; 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%26apos; 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.

• 出版日期2012-2