| Structural highlights
Function
[USB1_YEAST] Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 3'phosphate. Could be involved in aerobic respiration.[HAMAP-Rule:MF_03040][1] [2] [3]
Publication Abstract from PubMed
U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.
Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.,Didychuk AL, Montemayor EJ, Carrocci TJ, DeLaitsch AT, Lucarelli SE, Westler WM, Brow DA, Hoskins AA, Butcher SE Nat Commun. 2017 Sep 8;8(1):497. doi: 10.1038/s41467-017-00484-w. PMID:28887445[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hazbun TR, Malmstrom L, Anderson S, Graczyk BJ, Fox B, Riffle M, Sundin BA, Aranda JD, McDonald WH, Chiu CH, Snydsman BE, Bradley P, Muller EG, Fields S, Baker D, Yates JR 3rd, Davis TN. Assigning function to yeast proteins by integration of technologies. Mol Cell. 2003 Dec;12(6):1353-65. PMID:14690591
- ↑ Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kucinski I, Ginalski K, Dziembowski A. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3' end modification. Genes Dev. 2012 Sep 1;26(17):1911-25. doi: 10.1101/gad.193169.112. Epub 2012 Aug , 16. PMID:22899009 doi:10.1101/gad.193169.112
- ↑ Hilcenko C, Simpson PJ, Finch AJ, Bowler FR, Churcher MJ, Jin L, Packman LC, Shlien A, Campbell P, Kirwan M, Dokal I, Warren AJ. Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia. Blood. 2012 Nov 27. PMID:23190533 doi:10.1182/blood-2012-10-461491
- ↑ Didychuk AL, Montemayor EJ, Carrocci TJ, DeLaitsch AT, Lucarelli SE, Westler WM, Brow DA, Hoskins AA, Butcher SE. Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities. Nat Commun. 2017 Sep 8;8(1):497. doi: 10.1038/s41467-017-00484-w. PMID:28887445 doi:http://dx.doi.org/10.1038/s41467-017-00484-w
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