DOI: 10.1101/502781Dec 20, 2018Paper

Spliceosomal Prp8 intein at the crossroads of protein and RNA splicing

BioRxiv : the Preprint Server for Biology
Cathleen M GreenMarlene Belfort


The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNAs. At its functional core lies the essential Prp8 protein. Across diverse eukaryotes, this protein cofactor of RNA catalysis harbors a self-splicing element, called an intein. Inteins in Prp8 are extremely pervasive and are found at seven different sites in various species. Here, we focus on the Prp8 intein from Cryptococcus neoformans, a human fungal pathogen. We solved the crystal structure of this intein, revealing structural homology among self-splicing sequences in eukaryotes, including Hedgehog protein. Working with the C. neoformans Prp8 intein in a reporter assay, we find that the biologically relevant divalent metals copper and zinc inhibit intein splicing, albeit by two different mechanisms. Copper likely stimulates reversible modifications on a catalytically important cysteine, whereas zinc binds via the same critical cysteine with a Kd of ~1 nM. An intein-containing Prp8 precursor model is presented, suggesting that metal-induced protein splicing inhibition would disturb function of both Prp8 and the spliceosome. These results indicate that Prp8 protein splicing can be modulated, and that this could alter spliceosome function and ...Continue Reading

Related Concepts

Cryptococcus neoformans
RNA Splicing
RNA, Messenger
Protein S
Zinc-binding protein

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.