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The LARP1 La-Module recognizes both ends of TOP mRNAs
Hiba A Al-Ashtal1, Courtney M Rubottom1, Thomas C Leeper2
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
RNA Biology
|October 12, 2019
Summary
La-Related Protein 1 (LARP1) binds messenger RNAs (mRNAs) with 5'-terminal oligopyrimidine (TOP) motifs. The LARP1 N-terminal La-Module recognizes these TOP motifs and poly(A) RNA, suggesting a role in regulating mRNA translation and stability.
Area of Science:
- Molecular Biology
- RNA Biology
- Gene Regulation
Background:
- La-Related Protein 1 (LARP1) is a key RNA-binding protein.
- LARP1 regulates the stability and translation of specific messenger RNAs (mRNAs) that contain a 5'-terminal oligopyrimidine (TOP) motif.
- These TOP mRNAs encode essential components of the cellular translation machinery.
Purpose of the Study:
- To elucidate the function of the N-terminal La-Module of LARP1 in recognizing and regulating TOP mRNAs.
- To investigate the binding capabilities of the LARP1 La-Module beyond its known role in repressing TOP mRNA translation via the C-terminal DM15 region.
Main Methods:
- RNA-binding assays to determine the interaction of the LARP1 La-Module with TOP motifs and poly(A) RNA.
- Investigating cap-independent binding mechanisms.
- Analyzing the simultaneous binding capacity of the La-Module to different RNA elements.
Main Results:
- The LARP1 La-Module binds to 5'-terminal oligopyrimidine (TOP) motifs in a cap-independent manner.
- The La-Module also recognizes and binds to poly(A) RNA.
- Demonstrated that the LARP1 La-Module can bind simultaneously to both TOP motifs and poly(A) RNA.
Conclusions:
- The N-terminal La-Module of LARP1 plays a direct role in recognizing TOP mRNA motifs.
- LARP1's ability to bind both TOP motifs and poly(A) RNA suggests a novel mechanism for coordinating mRNA translation and stability.
- These findings provide new insights into the regulatory functions of LARP1 in gene expression.
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