High impact information on SUB2

• The essential yeast proteins Yra1 and Sub2 are messenger RNA export factors that have conserved counterparts in metazoans, designated Aly and UAP56, respectively [1].
• Here, we report a genetic interaction between YRA1 and SUB2, the gene for a DEAD box helicase involved in splicing [2].
• We tested the predictions that the yeast UAP56 homolog, SUB2, is required for the same step and functions collaboratively with MUD2, the yeast homolog of U2AF65 [3].
• In conjunction with previous studies, we conclude that at least two DExD/H box proteins, Prp5p and yUAP/Sub2p, mediate the U2 snRNP-branchpoint interaction [4].
• Data reported here as well as in the accompanying papers strongly implicate Sub2p in multiple steps of the spliceosome assembly process [5].

Biological context of SUB2

• The ability of a pre-mRNA splicing factor to suppress the hyperrecombination phenotype of a defective PolII complex raises the possibility of integrating transcription, RNA processing, and genome stability or a second role for SUB2 [6].
• These studies have uncovered a role for SUB2 in preventing genome instability [6].
• Suppression of plasmid instability in hpr1Delta can also be achieved by high-copy expression of the RNA splicing factor SUB2, which has recently been proposed to function in mRNA export, in addition to its role in pre-mRNA splicing [7].
• The genomic instability observed in sub2 mutants can be suppressed by high-copy-number HPR1 [6].
• Yra1p and Sub2p are components of the TREX complex, which couples transcription elongation with nuclear export of mRNAs [8].

Anatomical context of SUB2

• In Saccharomyces cerevisiae, overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells, yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional elongation [9].

Physical interactions of SUB2

• Yra1p also binds Sub2p, a DEAD box ATPase/RNA helicase implicated in splicing and required for mRNA export [10].
• We propose that Sub2 functionally interacts with Mud2 both before and after PS formation [3].
• Indeed, we find that a pool of heat shock HSP104 transcripts are 3'-end truncated in THO complex mutant as well as sub2 mutant backgrounds [9].

Other interactions of SUB2

• Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p [10].
• Genetic assays show cells that overexpress SUB2 from a high copy plasmid exhibit increased survival rates when selecting for a telomere-silenced URA3 reporter [11].
• Strikingly, an intronless transcript, HSP104, also accumulates in nuclei, suggesting that Sub2p function is not restricted to splicing events [12].
• Here, we report a genetic interaction between Yra1p and a conserved protein Sac3p, which previously was found to interact with Sub2p [8].
• Yeast THO1 and SUB2 (Saccharomyces cerevisiae) were identified as multicopy suppressors of the expression defects of the hpr1Delta mutant of THO [13].

Analytical, diagnostic and therapeutic context of SUB2

• A modified chromatin immunoprecipitation assay that includes an RNase step indicates that Sub2p is bound to nascent RNA, Yra1p is associated with both RNA and DNA, and Hpr1p is associated with DNA [14].

References