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Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase

By Mensur Dlakić and Arcady Mushegian


Prp8 is the largest and most highly conserved protein of the spliceosome, encoded by all sequenced eukaryotic genomes but missing from prokaryotes and viruses. Despite all evidence that Prp8 is an integral part of the spliceosomal catalytic center, much remains to be learned about its molecular functions and evolutionary origin. By analyzing sequence and structure similarities between Prp8 and other protein domains, we show that its N-terminal region contains a putative bromodomain. The central conserved domain of Prp8 is related to the catalytic domain of reverse transcriptases (RTs) and is most similar to homologous enzymes encoded by prokaryotic retroelements. However, putative catalytic residues in this RT domain are only partially conserved and may not be sufficient for the nucleotidyltransferase activity. The RT domain is followed by an uncharacterized sequence region with relatives found in fungal RT-like proteins. This part of Prp8 is predicted to adopt an α-helical structure and may be functionally equivalent to diverse maturase/X domains of retroelements and to the thumb domain of retroviral RTs. Together with a previously identified C-terminal domain that has an RNaseH-like fold, our results suggest evolutionary connections between Prp8 and ancient mobile elements. Prp8 may have evolved by acquiring nucleic acid–binding domains from inactivated retroelements, and their present-day role may be in maintaining proper conformation of the bound RNA cofactors and substrates of the splicing reaction. This is only the second example—the other one being telomerase—of the RT recruitment from a genomic parasite to serve an essential cellular function

Topics: Bioinformatics
Publisher: Cold Spring Harbor Laboratory Press
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Provided by: PubMed Central
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