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U12-type spliceosomal complex

Definition

Target type: cellularcomponent

Any spliceosomal complex that forms during the splicing of a messenger RNA primary transcript to excise an intron; the series of U12-type spliceosomal complexes is involved in the splicing of the majority of introns that contain atypical AT-AC terminal dinucleotides, as well as other non-canonical introns. The entire splice site signal, not just the terminal dinucleotides, is involved in determining which spliceosome utilizes the site. [GOC:krc, GOC:mah, PMID:11574683, PMID:11971955]

The U12-type spliceosomal complex is a specialized molecular machinery that plays a critical role in the splicing of a subset of eukaryotic pre-messenger RNA (pre-mRNA) molecules, known as U12-dependent introns. This complex differs from the more common U2-type spliceosome in its composition and the specific intron sequences it recognizes. Here's a detailed breakdown of its cellular components:

**Core Spliceosomal snRNAs:**

* **U12 snRNA:** This small nuclear RNA is the hallmark of the U12-type spliceosome. It binds to the 5' splice site of U12-dependent introns, which typically have a 5' splice site consensus sequence of AT-AC.
* **U6atac snRNA:** Analogous to U6 snRNA in the U2-type spliceosome, U6atac snRNA is involved in catalysis and interacts with both the 5' and 3' splice sites.

**Spliceosomal Proteins:**

* **SF3b complex:** This protein complex is crucial for recognizing the branch point sequence within U12-dependent introns.
* **U2AF25:** This protein specifically recognizes the polypyrimidine tract (PPT) downstream of the branch point.
* **U12-specific factors:** Several proteins, such as U12-65K and U12-22K, are specifically associated with the U12-type spliceosome and contribute to its assembly and function.
* **General splicing factors:** The U12-type spliceosome also incorporates a number of general splicing factors that are shared with the U2-type spliceosome, including the U1 snRNP, the U4/U6.U5 tri-snRNP, and the Prp19 complex.

**Assembly and Function:**

The assembly of the U12-type spliceosome follows a similar stepwise process to the U2-type spliceosome, involving the sequential recruitment of various snRNPs and proteins. The U12 snRNP recognizes the 5' splice site, followed by the binding of SF3b and U2AF25 to the branch point and PPT, respectively. This leads to the formation of the pre-spliceosome complex. Subsequent steps involve the incorporation of U6atac snRNA, the U4/U6.U5 tri-snRNP, and other splicing factors, culminating in the formation of the mature catalytic spliceosome.

The U12-type spliceosome then catalyzes the removal of the U12-dependent intron through a two-step transesterification reaction, ultimately leading to the joining of the flanking exons and the production of mature mRNA.

**Significance:**

U12-dependent splicing plays a crucial role in the regulation of gene expression and cellular function. Mutations in the U12-type spliceosome or its components can lead to a range of human diseases, including developmental disorders, neurodegenerative diseases, and cancer. Furthermore, U12-dependent splicing is thought to be involved in the alternative splicing of specific pre-mRNAs, contributing to the diversity of protein isoforms found in the cell.

**In summary, the U12-type spliceosomal complex is a specialized splicing machinery that is essential for the proper processing of a select group of pre-mRNAs containing U12-dependent introns. Its unique composition and intricate assembly process ensure the precise and efficient removal of these introns, contributing to the generation of diverse protein isoforms and ultimately influencing cellular function and organismal development.**'
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Proteins (1)

ProteinDefinitionTaxonomy
Splicing factor 3B subunit 3A splicing factor 3B subunit 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15393]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
trichostatin atrichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCESantibiotic antifungal agent;
hydroxamic acid;
trichostatin
bacterial metabolite;
EC 3.5.1.98 (histone deacetylase) inhibitor;
geroprotector
tacrolimustacrolimus (anhydrous) : A macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.

Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
macrolide lactambacterial metabolite;
immunosuppressive agent
lactacystinlactam;
S-substituted L-cysteine
e 7107E 7107: has antineoplastic activity