Multiple links between transcription and splicing

Abstract

Transcription and pre-mRNA splicing are extremely complex multimolecular processes that involve protein-DNA, protein-RNA, and protein-protein interactions. Splicing occurs in the close vicinity of genes and is frequently cotranscriptional. This is consistent with evidence that both processes are coordinated and, in some cases, functionally coupled. This review focuses on the roles of cis-and trans-acting factors that regulate transcription, on constitutive and alternative splicing. We also discuss possible functions in splicing of the C-terminal domain (CTD) of the RNA polymerase II (pol II) largest subunit, whose participation in other key pre-mRNA processing reactions (capping and cleavage/polyadenylation) is well documented. Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation. The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes.

The regulatory code for transcriptional response diversity and its relation to genome structural properties in Arabidopsis thaliana

“…Interestingly, presence of the TATA-box also strongly correlates with a decreased number of introns in the downstream gene (number of introns for genes with TATA: 3.7, without: 5.9; p ¼ 1.9EÀ93). It is presently not clear whether this correlation indicates a direct coupling between transcription and splicing [37] or whether it originates from an indirect correlation via a common principle shaping the genome, such as possibly the breadth of response and the role of both properties in defining it as reported here.…”

Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

“…Our observation that RNA binding proteins, especially PTBP1, are common parts of transcription initiation, elongation, and termination complexes provides many opportunities for a role similar to SF2 in destabilizing R-loops. Additionally, other RNA binding proteins have been found or are thought to interact directly with transcription machinery such as PGC1-␣, CoAA, and hnRNP K (Kornblihtt et al 2004;Moumen et al 2005).…”

“…RNA binding proteins regulate many stages of RNA metabolism to help determine gene expression programs (for reviews, see Keene and Tenenbaum 2002;Hieronymus and Silver 2004). To prepare mRNA for export to and translation in the cytoplasm, many events including splicing, cleavage of the 3Ј end, and editing occur cotranscriptionally (Kornblihtt et al 2004;Aguilera 2005a). After transcription, the mRNA-protein complex may reorganize as it is exported to the cytoplasm and prepared for translation (Fairman et al 2004).…”

“…To prepare mRNA for export to and translation in the cytoplasm, many events including splicing, cleavage of the 3Ј end, and editing occur cotranscriptionally (Kornblihtt et al 2004;Aguilera 2005a). After transcription, the mRNA-protein complex may reorganize as it is exported to the cytoplasm and prepared for translation (Fairman et al 2004).…”

“…RNA binding proteins also influence transcription initiation (Kornblihtt et al 2004). In mammalian cells, numerous RNA binding proteins are associated with hypo-phosphorylated RNA Pol II or transcription factors (Michelotti et al 1995;Calvo and Manley 2001;Stains et al 2005).…”