Contrary to previous results, we find that Pds5B is essential for centromeric cohesion

iption requires the integrity of the carboxyl terminal domain of the RNAPII, which indicates that transcriptional elongation plays a critical role in the recruitment of pre-mRNA processing factors. This proposal is compatible with the view that speckles act as inhibitory sites where specific factors are actively sequestered when their functional repression is required. The essential splicing factor SRSF1 is sequestered into these regions upon the induction of stress through a mechanism dependent on the dynamic interaction of SRPK with stress chaperone complexes, including Hsp70 and Hsp90. Similarly, the MALAT1 large noncoding RNA has been proposed to regulate the phosphorylation-dependent dynamics of splicing factors and their equilibrium between nucleoplasm availability and nuclear speckle sequestration. Linking transcriptional elongation control to this model, the 7SK small ncRNA, which is a scaffold component of transcription elongation CDK9-CycT1 inactive complexes together with HEXIM proteins, has been proposed to function, at least partially, by sequestering Polymerase Transcription factor Termination Birinapant manufacturer factory Initiation Transcript Elongation of a gene unit, integrated into the context of these structures Finally, what is the functional relationship between transcription factories and other nuclear compartments related to the biogenesis of the mRNA 3. Nuclear Speckles and the Regulation of Transcription and Pre-mRNA Processing Many independent studies in the last two decades have led to a model in which the maturation of nascent transcripts take place simultaneously to their synthesis, that is, cotranscriptionally. This may be specific to a subset of genes or even to specific introns of a gene and is therefore considered not to be strictly required for the completion of pre-mRNA processing itself. However, cotranscriptional processing allows for the functional coupling of the different steps of RNA biogenesis. The bidirectional interdependence among chromatin conformation and posttranslational modifications, in both transcription and different steps of pre-mRNA processing, constitutes an additional layer in gene expression regulation. Moreover, it may play a pivotal role in complex processes, such as neuronal differentiation and activity, global integration of RNA processing signatures and DNA damage, and developmental programs. If pre-mRNA processing is performed largely in a regulated cotranscriptional fashion, the dynamic distribution of pre-mRNA processing factors should be correlated with the organization of transcriptionally active sites in the nucleus. The distribution of pre-mRNA processing factors in the eukaryotic nucleus, as observed using immunofluorescence 4 Genetics Research International Recycling/assembly Active locus IGCs Positive elongation complex IGCs Active locus Pre mRNA Intron Transcription factory Negative elongation complex mRNP assembly and export; surveillance IGCs IGCs Active locus Inactive locus Pre mRNA Cotranscriptional splicing Posttranscriptional splicing Regulatory ncRNA these inactive P-TEFb complexes at nuclear speckles. However, there is currently little information known about the actual relevance of these dynamic interactions regarding the response of the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19818408 cell to specific stimuli or its correlation with changes in transcriptomic profiles. For example, PTEFb components colocalize at nuclear speckles with these negative regulators and also with the transcription activator adaptor Brd4. Rigorous