U1 spliceosomal RNA
|U1 spliceosomal RNA|
|Predicted secondary structure and sequence conservation of U1|
|RNA type||Gene; snRNA; splicing|
|GO||0000368 0030627 0005685|
U1 spliceosomal RNA is the small nuclear RNA (snRNA) component of U1 snRNP (small nuclear ribonucleoprotein), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. Splicing, or the removal of introns, is a major aspect of post-transcriptional modification, and takes place only in the nucleus of eukaryotes.
Structure and function
In humans, the U1 spliceosomal RNA is 164 bases long, forms four stem-loops, and possesses a 5'-trimethylguanosine five-prime cap. Bases 3 to 10 are a conserved sequence that base-pairs with the 5' splice site of introns during RNA splicing, and bases 126 to 133 form the Sm site, around which the Sm ring is assembled. Stem-loop I binds to the U1-70K protein, stem-loop II binds to the U1 A protein, stem-loops III and IV bind to the core RNP domain, a heteroheptameric Sm ring consisting of SmB/B', SmD1/2/3, SmE, SmF, and SmG. U1 C interacts primarily through protein-protein interactions.
Experimentation has demonstrated that the binding of U1 snRNA to the 5'-splice site is required, but not sufficient, to begin spliceosome assembly.
There are significant differences in sequence and secondary structure between metazoan and yeast U1 snRNAs, the latter being much longer (568 nucleotides as compared to 164 nucleotides in humans). Nevertheless, secondary structure predictions suggest that all U1 snRNAs share a 'common core' consisting of helices I, II, the proximal region of III, and IV. This family does not contain the larger yeast sequences.
A non-canonical role for U1 snRNP has recently been described in the regulation of alternative polyA site selection It is proposed that increased transcription rates "sponge" U1 snRNP, decreasing its availability. This model is supported experimentally, as reducing U1 snRNP levels with antisense morpholino oligonucleotides led to a dose-dependent shift of polyA usage to generate shorter mRNA transcripts.
- Nagai, K; Muto, Y; Pomeranz Krummel, DA; Kambach, C; Ignjatovic, T; Walke, S; Kuglstatter, A (May 2001). "Structure and assembly of the spliceosomal snRNPs. Novartis Medal Lecture.". Biochemical Society Transactions 29 (Pt 2): 15–26. doi:10.1042/0300-5127:0290015. PMID 11356120. Retrieved 17 December 2014.
- Stark, Holger; Dube, Prakash; Lührmann, Reinhard; Kastner, Berthold (25 January 2001). "Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle". Nature 409 (6819): 539–542. doi:10.1038/35054102. PMID 11206553. Retrieved 17 December 2014.
- Weaver, Robert F. (2005). Molecular Biology, p.433. McGraw-Hill, New York, NY. ISBN 0-07-284611-9.
- Zwieb, C (1997). "The uRNA database". Nucleic Acids Res 25 (1): 102–103. doi:10.1093/nar/25.1.102. PMC 146409. PMID 9016512.
- Berg MG, Singh LN, Younis I, Liu Q, Pinto AM, Kaida D, Zhang Z, Cho S, Sherrill-Mix S, Wan L, Dreyfuss G (Jul 2012). "U1 snRNP determines mRNA length and regulates isoform expression". Cell 150 (1): 53–64. doi:10.1016/j.cell.2012.05.029. PMC 3412174. PMID 22770214.
- Oubridge, C; Ito N; Evans PR; Teo CH; Nagai K (1994). "Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin". Nature 372 (6505): 432–438. doi:10.1038/372432a0. PMID 7984237.
- Katsamba, PS; Myszka DG; Laird-Offringa IA (2001). "Two functionally distinct steps mediate high affinity binding of U1A protein to U1 hairpin II RNA". J Biol Chem 276 (24): 21476–21481. doi:10.1074/jbc.M101624200. PMID 11297556.