Structural highlights
Function
ISY1_YEAST Involved in pre-mRNA splicing and cell cycle control. As a component of the NTC complex (or PRP19-associated complex), associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. The cell cycle arrest of SYF2 defective cells may be due to the inefficient splicing of TUB1. Also involved in DNA repair.[1] [2] [3]
Publication Abstract from PubMed
Pre-mRNA splicing proceeds by two consecutive trans-esterification reactions via a lariat-intron intermediate. We present the 3.8 A cryo-EM structure of the spliceosome immediately after lariat formation. The 5'-splice site is cleaved but remains close to the catalytic Mg2+ site in the U2/U6 snRNA triplex, and the 5'-phosphate of the intron nucleotide G(+1) is linked to the branch adenosine 2'OH. The 5'-exon is held between the Prp8 amino-terminal and Linker domains, and base-pairs with U5 snRNA loop 1. Non-Watson-Crick interactions between the branch helix and 5'-splice site dock the branch adenosine into the active site, while intron nucleotides +3 to +6 base-pair with the U6 snRNA ACAGAGA sequence. Isy1 and the step one factors Yju2 and Cwc25 stabilise docking of the branch helix. The intron downstream of the branch site emerges between the Prp8 reverse transcriptase (RT) and Linker domains and extends towards the Prp16 helicase, suggesting a plausible mechanism of remodelling before exon ligation.
Cryo-EM structure of the spliceosome immediately after branching.,Galej WP, Wilkinson ME, Fica SM, Oubridge C, Newman AJ, Nagai K Nature. 2016 Jul 26. doi: 10.1038/nature19316. PMID:27459055[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dix I, Russell C, Yehuda SB, Kupiec M, Beggs JD. The identification and characterization of a novel splicing protein, Isy1p, of Saccharomyces cerevisiae. RNA. 1999 Mar;5(3):360-8. PMID:10094305
- ↑ Chen CH, Tsai WY, Chen HR, Wang CH, Cheng SC. Identification and characterization of two novel components of the Prp19p-associated complex, Ntc30p and Ntc20p. J Biol Chem. 2001 Jan 5;276(1):488-94. PMID:11018040 doi:http://dx.doi.org/10.1074/jbc.M006958200
- ↑ Dahan O, Kupiec M. Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint. Nucleic Acids Res. 2002 Oct 15;30(20):4361-70. PMID:12384582
- ↑ Galej WP, Wilkinson ME, Fica SM, Oubridge C, Newman AJ, Nagai K. Cryo-EM structure of the spliceosome immediately after branching. Nature. 2016 Jul 26. doi: 10.1038/nature19316. PMID:27459055 doi:http://dx.doi.org/10.1038/nature19316
