Abstract
The U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs) are components of the spliceosome, which catalyzes pre-mRNA splicing. One of the largest and the most highly conserved proteins in the spliceosome is Prp8p, a component of the U5 snRNP. Despite its size and conservation, very few motifs have been identified that suggest specific biochemical functions. A variant of the Jab1/MPN domain found in a class of deubiquitinating enzymes is present near the C terminus of Prp8p. Ubiquitination regulates a broad range of cellular pathways, and its functions generally require ubiquitin recognition by one or more ubiquitin-binding domains (UBDs). No precise role for ubiquitin has been defined in the pre-mRNA splicing pathway, and no known UBDs have been found within splicing proteins. Here we show that a Prp8p fragment containing the Jab1/MPN domain binds directly to ubiquitin with an affinity comparable to other known UBDs. Several mutations within this domain that compromise splicing also reduce interaction of the fragment with ubiquitin-Sepharose. Our results define a new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing machinery.
References
65
Referenced
67
10.1128/MCB.18.11.6756
/ Mol. Cell. Biol. (1998)10.1371/journal.pbio.0020002
10.1093/genetics/154.1.61
/ Genetics (2000)10.1016/0076-6879(89)80111-9
10.1534/genetics.105.042044
10.1146/annurev.genet.36.043002.091635
10.1002/j.1460-2075.1992.tb05457.x
/ EMBO J. (1992)10.1101/gad.13.15.1970
10.1126/science.1075901
10.1017/S1355838201016077
10.1038/nature00935
10.1038/376745a0
{'key': '2021112105403391000_12.2.292.13', 'first-page': '1554', 'volume': '7', 'year': '2001', 'journal-title': 'RNA'}
/ RNA (2001)10.1261/rna.2220705
{'key': '2021112105403391000_12.2.292.15', 'first-page': '1', 'volume': '194', 'year': '1991', 'journal-title': 'Methods Enzymol.'}
/ Methods Enzymol. (1991)10.1016/S0021-9258(19)75933-X
/ J. Biol. Chem. (1987)10.1074/jbc.M102755200
10.1038/nrm1701
10.1002/yea.320110406
10.1016/S1097-2765(03)00270-3
10.1016/S0006-291X(03)01009-X
10.18388/abp.1998_4346
/ Acta Biochim. Pol. (1998){'key': '2021112105403391000_12.2.292.23', 'first-page': '260', 'volume': '1', 'year': '1995', 'journal-title': 'RNA'}
/ RNA (1995)10.1093/genetics/155.4.1667
/ Genetics (2000)10.1016/S1097-2765(00)80175-6
10.1073/pnas.102304299
10.1021/bi971296x
10.1128/MCB.19.3.2008
/ Mol. Cell. Biol. (1999)10.1126/science.1077783
10.1093/emboj/20.10.2553
10.1038/sj.emboj.7600241
10.1186/1471-2091-3-28
/ BMC Biochem. (2002)10.1074/jbc.M212353200
10.1002/j.1460-2075.1996.tb00810.x
/ EMBO J. (1996)10.1038/nsb906
10.1038/nbt849
10.1093/emboj/21.10.2397
10.1016/S1097-2765(04)00217-5
10.1038/nsmb962
10.1016/S0960-9822(07)00345-4
10.1101/gr.473902
{'key': '2021112105403391000_12.2.292.42', 'first-page': '213', 'volume': '2', 'year': '1996', 'journal-title': 'RNA'}
/ RNA (1996)10.1017/S1355838299981785
10.1101/gad.13.15.1983
10.1073/pnas.93.24.13641
10.1074/jbc.M103248200
10.1016/S0092-8674(00)80925-3
10.1073/pnas.96.13.7226
{'key': '2021112105403391000_12.2.292.49', 'first-page': '1543', 'volume': '7', 'year': '2001', 'journal-title': 'RNA'}
/ RNA (2001)10.1126/science.7770774
10.1016/S1097-2765(04)00129-7
10.1002/j.1460-2075.1995.tb07258.x
/ EMBO J. (1995)10.1093/nar/23.3.320
10.1074/jbc.M400023200
10.1021/bi035033g
10.1101/gad.9.7.855
{'key': '2021112105403391000_12.2.292.57', 'first-page': '584', 'volume': '1', 'year': '1995', 'journal-title': 'RNA'}
/ RNA (1995)10.1093/genetics/143.2.723
/ Genetics (1996)10.1093/genetics/157.4.1451
/ Genetics (2001)10.1016/S0092-8674(01)00387-7
10.1126/science.1075898
10.1073/pnas.87.6.2216
10.1016/S0022-2836(02)01145-2
10.1016/j.cub.2004.11.058
10.1038/nature01071
Dates
Type | When |
---|---|
Created | 19 years, 7 months ago (Jan. 20, 2006, 4:28 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 21, 2021, 8:45 a.m.) |
Indexed | 1 year ago (Sept. 2, 2024, 1:50 a.m.) |
Issued | 19 years, 7 months ago (Jan. 20, 2006) |
Published | 19 years, 7 months ago (Jan. 20, 2006) |
Published Online | 19 years, 7 months ago (Jan. 20, 2006) |
Published Print | 19 years, 7 months ago (Feb. 1, 2006) |
@article{BELLARE_2006, title={Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p}, volume={12}, ISSN={1469-9001}, url={http://dx.doi.org/10.1261/rna.2152306}, DOI={10.1261/rna.2152306}, number={2}, journal={RNA}, publisher={Cold Spring Harbor Laboratory}, author={BELLARE, PRIYA and KUTACH, ALAN K. and RINES, AMY K. and GUTHRIE, CHRISTINE and SONTHEIMER, ERIK J.}, year={2006}, month=jan, pages={292–302} }