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Published on: July 14, 2015
RAP55: insights into an evolutionarily conserved protein family
Aline Marnef1, John Sommerville, Michael R Ladomery
1Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
The RAP55 protein family, including RAP55A and RAP55B, plays a conserved role in controlling mRNA translation and P-body formation across eukaryotes. Further research is needed to understand its connection to primary biliary cirrhosis (PBC).
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The RAP55 protein family is evolutionarily conserved in eukaryotes.
- Vertebrates possess two highly conserved paralogues: RAP55A and RAP55B, with distinct functional and expression profiles yet to be fully compared.
- RAP55 proteins contain conserved domains (LSm14, FDF motif, RGG repeats) crucial for their functions.
Purpose of the Study:
- To compare the functional properties and expression patterns of RAP55A and RAP55B paralogues.
- To elucidate the role of RAP55 proteins in mRNA translation control, mRNP particle incorporation, and P-body/stress granule localization.
- To investigate the potential link between human RAP55A, P-bodies, and primary biliary cirrhosis (PBC).
Main Methods:
- Bioinformatic analysis of conserved domains within the RAP55 protein family.
- Localization studies of RAP55A in P-body-like complexes in germline and somatic cells.
- Analysis of Xenopus laevis RAP55B within translationally repressed mRNP complexes in oocytes.
Main Results:
- RAP55 proteins possess multiple domains (LSm14, FDF, RGG repeats) mediating translational repression, mRNP incorporation, protein interactions, and P-body/stress granule localization.
- All investigated RAP55A proteins localize to P-body-like structures in both germline and somatic cells.
- Xenopus laevis RAP55B is associated with translationally repressed mRNP complexes in early oocytes.
Conclusions:
- The RAP55 protein family has evolved a fundamental and conserved role in regulating mRNA translation.
- RAP55A is identified as an autoantigen in patients with primary biliary cirrhosis (PBC).
- The precise relationship between RAP55A, P-bodies, and PBC pathogenesis requires further investigation.
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