The isolated La-module of LARP1 mediates 3’ poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1
| Autor: | Kalle Gehring, Guennadi Kozlov, Richard J. Maraia, Bruno D. Fonseca, Sergei Gaidamakov, Sandy Mattijssen, Amitabh Ranjan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Polyadenylation
RNA Stability Protein domain Biology Autoantigens Poly(A)-Binding Protein I Poly(A)-Binding Proteins 03 medical and health sciences 0302 clinical medicine PABPC1 Humans Protein Interaction Domains and Motifs RNA Messenger Nucleotide Motifs Molecular Biology 030304 developmental biology 0303 health sciences Binding Sites RNA recognition motif fungi Cell Biology MRNA stabilization Toll-Like Receptor 2 LARP1 Cell biology HEK293 Cells Ribonucleoproteins Toll-Like Receptor 9 030220 oncology & carcinogenesis Oligopeptides Linker Protein Binding Research Paper |
| Zdroj: | RNA Biol |
| ISSN: | 1555-8584 1547-6286 |
| Popis: | The protein domain arrangement known as the La-module, comprised of a La motif (LaM) followed by a linker and RNA recognition motif (RRM), is found in seven La-related proteins: LARP1, LARP1B, LARP3 (La protein), LARP4, LARP4B, LARP6, and LARP7 in humans. Several LARPs have been characterized for their distinct activity in a specific aspect of RNA metabolism. The La-modules vary among the LARPs in linker length and RRM subtype. The La-modules of La protein and LARP7 bind and protect nuclear RNAs with UUU-3ʹ tails from degradation by 3ʹ exonucleases. LARP4 is an mRNA poly(A) stabilization factor that binds poly(A) and the cytoplasmic poly(A)-binding protein PABPC1 (also known as PABP). LARP1 exhibits poly(A) length protection and mRNA stabilization similar to LARP4. Here, we show that these LARP1 activities are mediated by its La-module and dependent on a PAM2 motif that binds PABP. The isolated La-module of LARP1 is sufficient for PABP-dependent poly(A) length protection and mRNA stabilization in HEK293 cells. A point mutation in the PAM2 motif in the La-module impairs mRNA stabilization and PABP binding in vivo but does not impair oligo(A) RNA binding by the purified recombinant La-module in vitro. We characterize the unusual PAM2 sequence of LARP1 and show it may differentially affect stable and unstable mRNAs. The unique LARP1 La-module can function as an autonomous factor to confer poly(A) protection and stabilization to heterologous mRNAs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|