U11 spliceosomal RNA

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U11 spliceosomal RNA
U11 secondary structure.png
Secondary structure of human U11 spliceosomal RNA
Identifiers
SymbolU11
Rfam RF00548
Other data
RNA type Gene; snRNA; splicing
Domain(s) Eukaryota
GO GO:0000369 GO:0030627 GO:0005692
SO SO:0000398
PDB structures PDBe

The U11 snRNA (small nuclear ribonucleic acid) is an important non-coding RNA in the minor spliceosome protein complex, which activates the alternative splicing mechanism. The minor spliceosome is associated with similar protein components as the major spliceosome. It uses U11 snRNA to recognize the 5' splice site (functionally equivalent to U1 snRNA) while U12 snRNA binds to the branchpoint to recognize the 3' splice site (functionally equivalent to U2 snRNA). [1]

Contents

Secondary structure

U11 snRNA has a stem-loop structure with a 5' end as splice site sequence (5' ss) [2] and contains four stem loops structures (I-IV). A structural comparison of U11 snRNA between plants, vertebrates and insects shows that it is folded into a structure with a four-way junction at the 5' site and in a stem loop structure at the 3' site. [3]

Binding site during assembly pathway

The 5' splice site region possesses sequence complementarity with the 5' splice site of the eukaryotic U12 type pre-mRNA introns. Both the 5' splice site and the Sm binding site are highly conserved in all species. [3] Also, stem loop III is either a possible protein binding site or a base-pairing region since it has a highly conserved nucleotide sequence 'AUCAAGA'. [3]

Role during alternative splicing

Minor Spliceosome mechanism Minor Spliceosome mechanism.png
Minor Spliceosome mechanism

U11 and U12 snRNPs (minor spliceosomal pathway) are functional analogs of U1 and U2 snRNPs (major spliceosomal pathway) whereas the U4 atac/U6 atac snRNPs are similar to U4/U6. Unlike the major splicing pathway, U11 and U12 snRNPs bind to the mRNA as a stable, preformed U11/U12 di-snRNP complex. This is done through the use of seven proteins (65K, 59K, 48K, 35K, 31K, 25K and 20K). Four of them (59K, 48K, 35K and 25K) are associated with U11 snRNA. [4]

During the formation of the spliceosome, the 5' end of U11 and U12 snRNAs interact with the 5' splice site and branchpoint sequence of the mRNA respectively, through base pairing. [4] [5] U11 snRNP binds to a tandem repeat known as U11 snRNP-binding splicing enhancer (USSE) and initiates the splicing process. [6] Since both U11 and U12 snRNAs come together as a bicomplex, they form a molecular bridge between two ends of introns in the pre-spliceosomal complex. [4] The U11-48K and U11/U12-65K proteins recognize the splice site of U12 type intron and stabilize the U11/U12 bi-complex. [6] After activating the spliceosomal complex, U11 snRNA leaves the assembly.

This kind of 5' splice site recognition and intron bridging through protein-protein, protein-RNA and RNA-RNA interactions is unique in the minor splicesomal complex, unlike the major spliceosomal one. [4] Since alternative splicing is the key to the variation of gene expression (mRNA) encoding proteins, U11 is crucial to this regulatory process and responsible in forming a proteomic pool. Therefore U11 snRNA is important in terms of evolutionary aspects. [7]

Related Research Articles

RNA splicing Processing primary RNA to remove intron sequences and join the remaining exon sections

RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns and splicing back together exons. For nuclear-encoded genes, splicing occurs in the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually needed to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing occurs in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). There exist self-splicing introns, that is, ribozymes that can catalyze their own excision from their parent RNA molecule. The process of transcription, splicing and translation is called gene expression, the central dogma of molecular biology.

Spliceosome Molecular machine that removes intron RNA from the primary transcript

A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.

snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors or RNA polymerase II, and maintaining the telomeres.

Minor spliceosome

The minor spliceosome is a ribonucleoprotein complex that catalyses the removal (splicing) of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs in plants, insects, vertebrates and some fungi. This process is called noncanonical splicing, as opposed to U2-dependent canonical splicing. U12-type introns represent less than 1% of all introns in human cells. However they are found in genes performing essential cellular functions.

LSm

In molecular biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm proteins are defined by a characteristic three-dimensional structure and their assembly into rings of six or seven individual LSm protein molecules, and play a large number of various roles in mRNA processing and regulation.

U12 minor spliceosomal RNA

U12 minor spliceosomal RNA is formed from U12 small nuclear (snRNA), together with U4atac/U6atac, U5, and U11 snRNAs and associated proteins, forms a spliceosome that cleaves a divergent class of low-abundance pre-mRNA introns. Although the U12 sequence is very divergent from that of U2, the two are functionally analogous.

U1 spliceosomal RNA

U1 spliceosomal RNA is the small nuclear RNA (snRNA) component of U1 snRNP, 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.

U2 spliceosomal RNA

U2 spliceosomal snRNAs are a species of small nuclear RNA (snRNA) molecules found in the major spliceosomal (Sm) machinery of virtually all eukaryotic organisms. In vivo, U2 snRNA along with its associated polypeptides assemble to produce the U2 small nuclear ribonucleoprotein (snRNP), an essential component of the major spliceosomal complex. The major spliceosomal-splicing pathway is occasionally referred to as U2 dependent, based on a class of Sm intron—found in mRNA primary transcripts—that are recognized exclusively by the U2 snRNP during early stages of spliceosomal assembly. In addition to U2 dependent intron recognition, U2 snRNA has been theorized to serve a catalytic role in the chemistry of pre-RNA splicing as well. Similar to ribosomal RNAs (rRNAs), Sm snRNAs must mediate both RNA:RNA and RNA:protein contacts and hence have evolved specialized, highly conserved, primary and secondary structural elements to facilitate these types of interactions.

U4 spliceosomal RNA Non-coding RNA component of the spliceosome

The U4 small nuclear Ribo-Nucleic Acid is a non-coding RNA component of the major or U2-dependent spliceosome – a eukaryotic molecular machine involved in the splicing of pre-messenger RNA (pre-mRNA). It forms a duplex with U6, and with each splicing round, it is displaced from the U6 snRNA in an ATP-dependent manner, allowing U6 to re-fold and create the active site for splicing catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein Prp24 re-anneals U4 and U6. The crystal structure of a 5′ stem-loop of U4 in complex with a binding protein has been solved.

U6 spliceosomal RNA

U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP, 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 that catalyzes the excision of introns from pre-mRNA. Splicing, or the removal of introns, is a major aspect of post-transcriptional modification and takes place only in the nucleus of eukaryotes.

U4atac minor spliceosomal RNA

U4atac minor spliceosomal RNA is a ncRNA which is an essential component of the minor U12-type spliceosome complex. The U12-type spliceosome is required for removal of the rarer class of eukaryotic introns.

U6atac minor spliceosomal RNA

U6atac minor spliceosomal RNA is a non-coding RNA which is an essential component of the minor U12-type spliceosome complex. The U12-type spliceosome is required for removal of the rarer class of eukaryotic introns.

U2AF2 Protein-coding gene in the species Homo sapiens

Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.

SF3B1

Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene.

SF3B2

Splicing factor 3B subunit 2 is a protein that in humans is encoded by the SF3B2 gene.

SF3B4 Protein-coding gene in the species Homo sapiens

Splicing factor 3B subunit 4 is a protein that in humans is encoded by the SF3B4 gene.

PRPF4 Protein-coding gene in the species Homo sapiens

U4/U6 small nuclear ribonucleoprotein Prp4 is a protein that in humans is encoded by the PRPF4 gene. The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. PRPF4 is 1 of several proteins that associate with U4 and U6 snRNPs.[supplied by OMIM]

Prp8

Prp8 refers to both the Prp8 protein and Prp8 gene. Prp8's name originates from its involvement in pre-mRNA processing. The Prp8 protein is a large, highly conserved, and unique protein that resides in the catalytic core of the spliceosome and has been found to have a central role in molecular rearrangements that occur there. Prp8 protein is a major central component of the catalytic core in the spliceosome, and the spliceosome is responsible for splicing of precursor mRNA that contains introns and exons. Unexpressed introns are removed by the spliceosome complex in order to create a more concise mRNA transcript. Splicing is just one of many different post-transcriptional modifications that mRNA must undergo before translation. Prp8 has also been hypothesized to be a cofactor in RNA catalysis.

Kiyoshi Nagai Japanese structural biologist

Kiyoshi Nagai was a Japanese structural biologist at the MRC Laboratory of Molecular Biology Cambridge, UK. He was known for his work on the mechanism of RNA splicing and structures of the spliceosome.

References

  1. ↑ Elliot, David; Ladomery, Michael (2011). Molecular Biology of RNA. Oxford University Press. p. 124.
  2. ↑ Russell AG, Charette JM, Spencer DF, Gray MW (October 2006). "An early evolutionary origin for the minor spliceosome". Nature. 443 (7113): 863–6. Bibcode:2006Natur.443..863R. doi:10.1038/nature05228. PMID   17051219. S2CID   4419061.
  3. 1 2 3 Schneider C, Will CL, Brosius J, Frilander MJ, Lührmann R (June 2004). "Identification of an evolutionarily divergent U11 small nuclear ribonucleoprotein particle in Drosophila" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 101 (26): 9584–9. Bibcode:2004PNAS..101.9584S. doi: 10.1073/pnas.0403400101 . PMC   470718 . PMID   15210936.
  4. 1 2 3 4 Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R (June 2004). "The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome". RNA. 10 (6): 929–41. doi:10.1261/rna.7320604. PMC   1370585 . PMID   15146077.
  5. ↑ Kolossova I, Padgett RA (March 1997). "U11 snRNA interacts in vivo with the 5' splice site of U12-dependent (AU-AC) pre-mRNA introns". RNA. 3 (3): 227–33. PMC   1369475 . PMID   9056760.
  6. 1 2 Verbeeren J, Niemelä EH, Turunen JJ, Will CL, Ravantti JJ, Lührmann R, Frilander MJ (March 2010). "An ancient mechanism for splicing control: U11 snRNP as an activator of alternative splicing". Molecular Cell. 37 (6): 821–33. doi:10.1016/j.molcel.2010.02.014. hdl: 11858/00-001M-0000-0012-D5F2-D . PMID   20347424.
  7. ↑ Kashyap, Luv; Tripathi Parul. "Alternative splicing: How one gene can make many proteins" (PDF). Bioscience Explained.
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