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From Proteopedia
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==Role in Pre-mRNA splicing== | ==Role in Pre-mRNA splicing== | ||
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| + | The processing of [http://en.wikipedia.org/wiki/Pre-mRNA pre-mRNA] takes place through the use of a large dynamic machine known as the [http://en.wikipedia.org/wiki/Spliceosome spliceosome], through which [http://en.wikipedia.org/wiki/Intron introns] are removed and [http://en.wikipedia.org/wiki/Exon exons] are spliced together to create a mature [http://en.wikipedia.org/wiki/MRNA mRNA]<ref name ="architecture of"/> | ||
| + | <ref name ="structure and function">PMID:19000813</ref>. The spliceosome is comprised of five [http://en.wikipedia.org/wiki/SnRNA snRNA]] molecules (snRNAs U1, U2, U4, U5, and U6)and over one hundred associated proteins<ref name ="architecture of"/><ref name ="structure and function"/>. Assembly of the spliceosome is thought to take place in a stepwise manner around the pre-mRNA transcript<ref name ="architecture of"/><ref name ="structure and function"/>. The first step involves recognition of the 5’ splice site by U1 [http://en.wikipedia.org/wiki/SnRNP snRNP], followed by recognition of the branch point sequence by U2 snRNP<ref name ="architecture of"/><ref name ="structure and function"/>. From this point the remaining snRNPs U4, U5, and U6 join as a preformed tri-snNRP<ref name ="architecture of"/><ref name ="structure and function"/>. Together the five snRNPs for the precatalytic spliceosome which must undergo a series of changes before it can actively splice<ref name ="structural evidence">PMID:19525970</ref><ref name ="structure and function"/><ref name ="common design">PMID:19525970</ref><ref name ="architecture of">PMID:22471593</ref>. | ||
The Lsm complex 2-8 is involved in pre-mRNA splicing through association with the 3’terminal poly(U) tract of U6 snRNA. While the exact mechanism by which it acts is unclear it is thought that the Lsm 2-8 complex provides stability and function to the U6 snRNP. For example, several experiments using mutants with point mutations of the Lsm proteins 2-8 have shown defects in splicing that correlate with low levels of U6 snRNA. It may also play a role in the various rearrangements that are necessary throughout the splicing cycle. In fact, it has been shown to be important in the assembly of U4-U6 di snRNP and U4-U5/U6 tri snRNP (He). | The Lsm complex 2-8 is involved in pre-mRNA splicing through association with the 3’terminal poly(U) tract of U6 snRNA. While the exact mechanism by which it acts is unclear it is thought that the Lsm 2-8 complex provides stability and function to the U6 snRNP. For example, several experiments using mutants with point mutations of the Lsm proteins 2-8 have shown defects in splicing that correlate with low levels of U6 snRNA. It may also play a role in the various rearrangements that are necessary throughout the splicing cycle. In fact, it has been shown to be important in the assembly of U4-U6 di snRNP and U4-U5/U6 tri snRNP (He). | ||
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=References= | =References= | ||
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Revision as of 20:28, 4 July 2012
Lsm
by Kelly Hrywkiw Template:STRUCTURE 4emg
Contents |
Introduction
Sm-like (Lsm) proteins most closely resemble Sm proteins, both of which are found in all three domains of life (Wu). Sm proteins play a large role in spliceosome biogenesis through mediating U1, U2, U4, U5, and U6 snRNP assembly. The Sm proteins can be broken down into seven specific proteins (SmB, SmD1, SmD2, SmD3, SmE, SmF, and SmG in humans) all of which share a conserved Sm motif. The Lsm proteins also share the Sm motif, with a total of nine specific Lsm proteins found in yeast (Lsm1-Lsm9). The Lsm proteins 2-7 most closely resemble Sm proteins D1-G, where Lsm 1 and 8 most closely resemble the SmB proteins (He). Lsm9 does not appear to resemble any of the Sm proteins, although there have been some related structures found in the archaeal genome (He). Several studies have shown that the Sm proteins form into seven membered rings which bind to the sm binding site, a U rich sequence found in all but U6 snRNA. Similarly, Lsm proteins have been found to associate into three complexes, Lsm2-8, Lsm1-7, and Lsm2-7 (Wu). The exact mechanisms of these complexes are dictated by their composition, structure, and cellular location and their overall functioning in pre-mRNA splicing, mRNA decay, and other additional roles (Wu) (He).
Role in Pre-mRNA splicing
The processing of pre-mRNA takes place through the use of a large dynamic machine known as the spliceosome, through which introns are removed and exons are spliced together to create a mature mRNA[1] [2]. The spliceosome is comprised of five snRNA] molecules (snRNAs U1, U2, U4, U5, and U6)and over one hundred associated proteins[1][2]. Assembly of the spliceosome is thought to take place in a stepwise manner around the pre-mRNA transcript[1][2]. The first step involves recognition of the 5’ splice site by U1 snRNP, followed by recognition of the branch point sequence by U2 snRNP[1][2]. From this point the remaining snRNPs U4, U5, and U6 join as a preformed tri-snNRP[1][2]. Together the five snRNPs for the precatalytic spliceosome which must undergo a series of changes before it can actively splice[3][2][4][1].
The Lsm complex 2-8 is involved in pre-mRNA splicing through association with the 3’terminal poly(U) tract of U6 snRNA. While the exact mechanism by which it acts is unclear it is thought that the Lsm 2-8 complex provides stability and function to the U6 snRNP. For example, several experiments using mutants with point mutations of the Lsm proteins 2-8 have shown defects in splicing that correlate with low levels of U6 snRNA. It may also play a role in the various rearrangements that are necessary throughout the splicing cycle. In fact, it has been shown to be important in the assembly of U4-U6 di snRNP and U4-U5/U6 tri snRNP (He).
Role in mRNA decay
Other roles of Lsm proteins
Structure of Lsm proteins
Lsm 3
Lsm 4
Lsm5
Lsm 5/6/7
Additional Resources
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 van der Feltz C, Anthony K, Brilot A, Pomeranz Krummel DA. Architecture of the Spliceosome. Biochemistry. 2012 Apr 10. PMID:22471593 doi:10.1021/bi201215r
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Sperling J, Azubel M, Sperling R. Structure and function of the Pre-mRNA splicing machine. Structure. 2008 Nov 12;16(11):1605-15. PMID:19000813 doi:10.1016/j.str.2008.08.011
- ↑ Zhang L, Xu T, Maeder C, Bud LO, Shanks J, Nix J, Guthrie C, Pleiss JA, Zhao R. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009 Jul;16(7):731-9. Epub 2009 Jun 14. PMID:19525970 doi:10.1038/nsmb.1625
- ↑ Zhang L, Xu T, Maeder C, Bud LO, Shanks J, Nix J, Guthrie C, Pleiss JA, Zhao R. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009 Jul;16(7):731-9. Epub 2009 Jun 14. PMID:19525970 doi:10.1038/nsmb.1625
