scholarly journals Phylogenetic Comparison and Splicing Analysis of U1 snRNP-specific Protein U1C in Eukaryotes

2021 ◽  
Author(s):  
Mo-Xian Chen ◽  
Kai-Lu Zhang ◽  
Jian-Li Zhou ◽  
Jing-Fang Yang ◽  
Yu-Zhen Zhao ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Expression Profiles ◽  
Specific Protein ◽  
Comprehensive Overview ◽  
Small Nuclear Ribonucleoprotein ◽  
U1 Snrnp ◽  
Multiple Copies ◽  
And Function ◽  
Nuclear Ribonucleoprotein ◽  
Site Recognition

Abstract As a pivotal regulator of 5’ splice site recognition, the U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to variety of diseases including cancer. However, phylogenetic relationship and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared to the homologs from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved, and is found in multiple copies in few members of U1C genes family. Furthermore, expression pattern showed that U1Cs have potential role in cancer progression and human development. In summary, our study presents a comprehensive overview of animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

scholarly journals Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes

2021 ◽  
Vol 8 ◽  
Author(s):  
Kai-Lu Zhang ◽  
Jian-Li Zhou ◽  
Jing-Fang Yang ◽  
Yu-Zhen Zhao ◽  
Debatosh Das ◽  
...  
Keyword(s):  
Gene Family ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Specific Protein ◽  
Comprehensive Overview ◽  
Small Nuclear Ribonucleoprotein ◽  
U1 Snrnp ◽  
Multiple Copies ◽  
And Function

As a pivotal regulator of 5’ splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

The spliceosome assembly pathway in mammalian extracts

1992 ◽  
Vol 12 (10) ◽  
pp. 4279-4287 ◽  
Author(s):  
S F Jamison ◽  
A Crow ◽  
M A Garcia-Blanco
Keyword(s):  
Spliceosome Assembly ◽  
Protein Factor ◽  
Small Nuclear Ribonucleoprotein ◽  
U2 Snrnp ◽  
U1 Snrnp ◽  
U2 Auxiliary Factor ◽  
Nuclear Ribonucleoprotein ◽  
Auxiliary Factor ◽  
First Time ◽  
Kinetics Of

A mammalian splicing commitment complex was functionally defined by using a template commitment assay. This complex was partially purified and shown to be a required intermediate for complex A formation. The productive formation of this commitment complex required both splice sites and the polypyrimidine tract. U1 small nuclear ribonucleoprotein (snRNP) was the only spliceosomal U snRNP required for this formation. A protein factor, very likely U2AF, is probably involved in the formation of the splicing commitment complex. From the kinetics of appearance of complex A and complex B, it was previously postulated that complex A represents a functional intermediate in spliceosome assembly. Complex A was partially purified and shown to be a required intermediate for complex B (spliceosome) formation. Thus, a spliceosome pathway is for the first time supported by direct biochemical evidence: RNA+U1 snRNP+?U2 auxiliary factor+?Y----CC+U2 snRNP+Z----A+U4/6,5 snRNPs+ beta----B.

Differential block of U small nuclear ribonucleoprotein particle interactions during in vitro splicing of adenovirus E1A transcripts containing abnormally short introns

1991 ◽  
Vol 11 (3) ◽  
pp. 1258-1269
Author(s):  
M Himmelspach ◽  
R Gattoni ◽  
C Gerst ◽  
K Chebli ◽  
J Stévenin
Keyword(s):  
Donor Site ◽  
Ribonucleoprotein Particle ◽  
Adenovirus E1a ◽  
Branch Site ◽  
Small Nuclear Ribonucleoprotein ◽  
U2 Snrnp ◽  
U1 Snrnp ◽  
The Common ◽  
Nuclear Ribonucleoprotein

We have studied the consequences of decreasing the donor site-branch site distance on splicing factor-splice site interactions by analyzing alternative splicing of adenovirus E1A pre-mRNAs in vitro. We show that the proximal 13S donor site has a cis-inhibiting effect on the 9S and 12S mRNA reactions when it is brought too close to the common branch site, suggesting that the factor interactions in the common 3' part of the intron are impaired by the U1 small nuclear ribonucleoprotein particle (snRNP) binding to the displaced 13S donor site. Further analysis of the interactions was carried out by studying complex assembly and the accessibility to micrococcal nuclease digestion of 5'-truncated E1A substrates containing only splice sites for the 13S mRNA reaction. A deletion which brings the donor site- branch site distance to 49 nucleotides, which is just below the minimal functional distance, results in a complete block of the U4-U5-U6 snRNP binding, whereas a deletion 15 nucleotides larger results in a severe inhibition of the formation of the U2 snRNP-containing complexes. Sequence accessibility analyses performed by using the last mini-intron-containing transcript demonstrate that the interactions of U2 snRNP with the branch site are strongly impaired whereas the initial bindings of U1 snRNP to the donor site and of specific factors to the 3' splice site are not significantly modified. Our results strongly suggest that the interaction of U1 snRNP with the donor site of a mini-intron is stable enough in vitro to affect the succession of events leading to U2 snRNP binding with the branch site.

scholarly journals The spliceosome assembly pathway in mammalian extracts.

1992 ◽  
Vol 12 (10) ◽  
pp. 4279-4287 ◽  
Author(s):  
S F Jamison ◽  
A Crow ◽  
M A Garcia-Blanco
Keyword(s):  
Spliceosome Assembly ◽  
Protein Factor ◽  
Small Nuclear Ribonucleoprotein ◽  
U2 Snrnp ◽  
U1 Snrnp ◽  
U2 Auxiliary Factor ◽  
Nuclear Ribonucleoprotein ◽  
Auxiliary Factor ◽  
First Time ◽  
Kinetics Of

A mammalian splicing commitment complex was functionally defined by using a template commitment assay. This complex was partially purified and shown to be a required intermediate for complex A formation. The productive formation of this commitment complex required both splice sites and the polypyrimidine tract. U1 small nuclear ribonucleoprotein (snRNP) was the only spliceosomal U snRNP required for this formation. A protein factor, very likely U2AF, is probably involved in the formation of the splicing commitment complex. From the kinetics of appearance of complex A and complex B, it was previously postulated that complex A represents a functional intermediate in spliceosome assembly. Complex A was partially purified and shown to be a required intermediate for complex B (spliceosome) formation. Thus, a spliceosome pathway is for the first time supported by direct biochemical evidence: RNA+U1 snRNP+?U2 auxiliary factor+?Y----CC+U2 snRNP+Z----A+U4/6,5 snRNPs+ beta----B.

scholarly journals Accumulation of a novel spliceosomal complex on pre-mRNAs containing branch site mutations.

1995 ◽  
Vol 15 (10) ◽  
pp. 5750-5756 ◽  
Author(s):  
P Champion-Arnaud ◽  
O Gozani ◽  
L Palandjian ◽  
R Reed
Keyword(s):  
Second Step ◽  
Apparent Effect ◽  
Ribonucleoprotein Particle ◽  
Branch Site ◽  
Small Nuclear Ribonucleoprotein ◽  
U2 Snrnp ◽  
U1 Snrnp ◽  
Nuclear Ribonucleoprotein ◽  
Branchpoint Sequence ◽  
Independent Reaction

Pre-mRNA assembles into spliceosomal complexes in the stepwise pathway E-->A-->B-->C. We show that mutations in the metazoan branchpoint sequence (BPS) have no apparent effect on E complex formation but block the assembly of the A complex and the UV cross-linking of U2 small nuclear ribonucleoprotein particle (snRNP) proteins. Unexpectedly, a novel complex, designated E*, assembles on pre-mRNAs containing BPS mutations. Unlike the E complex, the E* complex accumulates in the presence of ATP. U1 snRNP and U2AF, which are tightly bound to pre-mRNA in the E complex, are not tightly bound in the E* complex. Significantly, previous work showed that U1 snRNP and U2AF become destabilized from pre-mRNA after E complex assembly on normal pre-mRNAs. Thus, our data are consistent with a model in which there are two steps in the transition from the E complex to the A complex (E-->E*-->A). In the first step, U1 snRNP and U2AF are destabilized in an ATP-dependent, BPS-independent reaction. In the second step, the stable binding of U2 snRNP occurs in a BPS-dependent reaction.

scholarly journals Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5′ Splice Site Selection

2008 ◽  
Vol 28 (19) ◽  
pp. 5924-5936 ◽  
Author(s):  
AnYu Zhou ◽  
Alexander C. Ou ◽  
Aeri Cho ◽  
Edward J. Benz ◽  
Shu-Ching Huang
Keyword(s):  
Splice Site ◽  
Dependent Manner ◽  
Splice Site Selection ◽  
Exon 2 ◽  
Small Nuclear Ribonucleoprotein ◽  
U1 Snrnp ◽  
Nuclear Ribonucleoprotein ◽  
Dose Dependent ◽  
Selection Of

ABSTRACT RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically affected the expression of Bcl-x isoforms. RBM25 stimulated proapoptotic Bcl-xS 5′ splice site (5′ ss) selection in a dose-dependent manner, whereas its depletion caused the accumulation of antiapoptotic Bcl-xL. Furthermore, RBM25 specifically bound to Bcl-x RNA through a CGGGCA sequence located within exon 2. Mutation in this element abolished the ability of RBM25 to enhance Bcl-xS 5′ ss selection, leading to decreased Bcl-xS isoform expression. Binding of RBM25 was shown to promote the recruitment of the U1 small nuclear ribonucleoprotein particle (snRNP) to the weak 5′ ss; however, it was not required when a strong consensus 5′ ss was present. In support of a role for RBM25 in modulating the selection of a 5′ ss, we demonstrated that RBM25 associated selectively with the human homolog of yeast U1 snRNP-associated factor hLuc7A. These data suggest a novel mode for Bcl-xS 5′ ss activation in which binding of RBM25 with exonic element CGGGCA may stabilize the pre-mRNA-U1 snRNP through interactions with hLuc7A.

scholarly journals FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP

2015 ◽  
Vol 112 (28) ◽  
pp. 8608-8613 ◽  
Author(s):  
Yong Yu ◽  
Robin Reed
Keyword(s):  
Rna Polymerase Ii ◽  
Coupled System ◽  
Base Pairs ◽  
Fused In Sarcoma ◽  
Small Nuclear Ribonucleoprotein ◽  
U1 Snrnp ◽  
Rnap Ii ◽  
Nuclear Ribonucleoprotein ◽  
Antisense Morpholino ◽  
Lateral Sclerosis

Pre-mRNA splicing is coupled to transcription by RNA polymerase II (RNAP II). We previously showed that U1 small nuclear ribonucleoprotein (snRNP) associates with RNAP II, and both RNAP II and U1 snRNP are also the most abundant factors associated with the protein fused-in-sarcoma (FUS), which is mutated to cause the neurodegenerative disease amyotrophic lateral sclerosis. Here, we show that an antisense morpholino that base-pairs to the 5′ end of U1 snRNA blocks splicing in the coupled system and completely disrupts the association between U1 snRNP and both FUS and RNAP II, but has no effect on the association between FUS and RNAP II. Conversely, we found that U1 snRNP does not interact with RNAP II in FUS knockdown extracts. Moreover, using these extracts, we found that FUS must be present during the transcription reaction in order for splicing to occur. Together, our data lead to a model that FUS functions in coupling transcription to splicing via mediating an interaction between RNAP II and U1 snRNP.

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