The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation

  title={The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation},
  author={Hassan Jumaa and Peter J. Nielsen},
  journal={The EMBO Journal},
SRp20 is a member of the highly conserved SR family of splicing regulators. Using a variety of reporter gene constructs, we show that SRp20 regulates alternative splicing of its own mRNA. Overexpression of SRp20 results in a reduction in the level of exon 4‐skipped SRp20 transcripts and activates the production of transcripts containing exon 4. These exon 4‐included transcripts encode a truncated protein lacking the C‐terminal RS domain. We provide evidence that SRp20 probably enhances the… 
Regulation of SRp20 exon 4 splicing.
The Arabidopsis splicing factor SR1 is regulated by alternative splicing
It is reported here that alternative splicing regulates SR1 itself, and based on the regulated co-expression of SR1 transcripts, it is possible that some SR1 functions could be determined by the combinatorial action of the various isoforms.
Regulation of alternative splicing by SRrp86 through coactivation and repression of specific SR proteins.
It is shown that SRrp86 can activate SRp20 and repress SC35 in a dose-dependent manner both in vitro and in vivo, and regulation of SR protein activity, coupled with regulated protein expression, suggest that SRp86 may play a crucial role in determining tissue specific patterns of alternative splicing.
Antagonistic factors control the unproductive splicing of SC35 terminal intron
Using various minigene constructs containing the terminal retained intron and flanking exons, a number of exonic splicing enhancer elements responding specifically to SC35 are identified, and an inverse correlation between affinity of SC35 and enhancer strength is shown, which highlights the existence of a complex network of self- and cross-regulatory mechanisms between splicing regulators.
SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs
It is shown that overexpression of SC35 in HeLa cells results in a significant decrease of endogenous SC35 mRNA levels along with changes in the relative abundance ofSC35 alternatively spliced mRNAs.
Alternative Splicing of Intron 3 of the Serine/Arginine-rich Protein 9G8 Gene
These results, and the fact that the exon 3 and 4 ESE sequences are conserved in vertebrates, strongly suggest that the alternative splicing of intron 3 represents an important step in the regulation of the expression of 9G8.
SR Proteins Induce Alternative Exon Skipping through Their Activities on the Flanking Constitutive Exons
It is shown that SR protein-induced exon skipping depends on their prevalent actions on a flanking constitutive exon and requires collaboration of more than one SR protein, and may constitute a key strategy for synergism with other splicing regulators in establishing tissue-specific alternative splicing critical for cell differentiation programs.
Characterization of SRp46, a Novel Human SR Splicing Factor Encoded by a PR264/SC35 Retropseudogene
It is demonstrated, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.
Regulation of Splicing Factors by Alternative Splicing and NMD Is Conserved between Kingdoms Yet Evolutionarily Flexible
It is demonstrated that unproductive splicing of the splicing factor SRSF5 (SRp40) is conserved among all animals and even observed in fungi; this is a rare example of alternative splicing conserved between kingdoms, yet its effect is to trigger mRNA degradation.


Regulated expression and RNA processing of transcripts from the Srp20 splicing factor gene during the cell cycle
The results suggest that splicing could be regulated during the cell cycle and that this could be, at least in part, due to regulated expression of SR proteins.
General splicing factor SF2/ASF promotes alternative splicing by binding to an exonic splicing enhancer.
The general splicing factor SF2/ASF binds in a sequence-specific manner to a purine-rich exonic splicing enhancer (ESE) in the last exon of bovine growth hormone (bGH) pre-mRNA. More importantly,
Overexpression of the SR proteins ASF/SF2 and SC35 influences alternative splicing in vivo in diverse ways.
Unexpectedly, overexpression of SC35, but not ASF/SF2, resulted in substantial accumulation of the unspliced SV40 pre-mRNA, which was efficiently transported to the cytoplasm, suggesting that SC35 may play an unanticipated role in mRNA stability and/or transport.
Identification and characterization of three members of the human SR family of pre‐mRNA splicing factors.
Consistent with the postulated importance of SR proteins in alternative splicing in vivo, complex changes in the levels of mRNAs encoding the above SR proteins upon T cell activation are demonstrated, concomitant withChanges in the expression of alternatively spliced isoforms of CD44 and CD45.
SR proteins can compensate for the loss of U1 snRNP functions in vitro.
It is shown that addition of excess mixed SR proteins to a HeLa in vitro splicing system stimulates utilization of a novel 5' splice site within the intron of the standard adenovirus pre-mRNA substrate.
A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer.
It is shown that enhancer activity is exquisitely sensitive to changes in the sequence of a 9-nucleotide motif (GAGGAAGAA) even when its purine content is preserved, and independent regulation of the levels of SR proteins may contribute to the developmental regulation of exon inclusion.
The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice sites.
  • P. Zuo, J. Manley
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
Using UV crosslinking and gel shift assays, it is demonstrated that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs.
The Drosophila SR protein RBP1 contributes to the regulation of doublesex alternative splicing by recognizing RBP1 RNA target sequences.
It is shown that RBP1 target sequences within the dsx repeat region are required for the efficient splicing of dsX pre‐mRNA, and thatRBP1 contributes to the activation of female‐specific ds x splicing in vivo by recognizing the purine‐rich polypyrimidine tract of the female‐ specific 3′ splice site.
General splicing factors SF2 and SC35 have equivalent activities in vitro, and both affect alternative 5' and 3' splice site selection.
It is concluded that SF2 and SC35 are distinct splicing factors, but they display indistinguishable splicing activities in vitro.