The U11 snRNA (
small nuclear ribonucleic acid) is an important
non-coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-c ...
in the
minor spliceosome The minor spliceosome is a ribonucleoprotein complex that catalyses the removal ( splicing) of an atypical class of spliceosomal introns (U12-type) from messenger RNAs in some clades of eukaryotes. This process is called noncanonical splicing, as op ...
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein c ...
, 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
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, ...
) while
U12 snRNA
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 U ...
binds to the branchpoint to recognize the
3' splice site (functionally equivalent to
U2 snRNA
U2 spliceosomal snRNAs are a species of small nuclear RNA (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 assem ...
).
Secondary structure
U11 snRNA has a
stem-loop structure with a 5' end as
splice site sequence (5' ss)
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.
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.
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'.
Role during alternative splicing
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.
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.
U11 snRNP binds to a
tandem repeat
Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...
known as U11 snRNP-binding splicing enhancer (USSE) and initiates the splicing process.
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.
The U11-48K and U11/U12-65K proteins recognize the splice site of U12 type intron and stabilize the U11/U12 bi-complex.
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.
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.
References
External links
* {{Rfam, id=RF00548, name=U11 spliceosomal RNA
Small nuclear RNA
Spliceosome
RNA splicing