CDK9 and PP2A regulate RNA polymerase II transcription termination and coupled RNA maturation.

CDK9 is a kinase critical for the productive transcription of protein-coding genes by RNA polymerase II (pol II). As part of P-TEFb, CDK9 phosphorylates the carboxyl-terminal domain (CTD) of pol II and elongation factors, which allows pol II to elongate past the early elongation checkpoint (EEC) encountered soon after initiation. We show that, in addition to halting pol II at the EEC, loss of CDK9 activity causes premature termination of transcription across the last exon, loss of polyadenylation factors from chromatin, and loss of polyadenylation of nascent transcripts.

hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles.

Alternative cleavage and polyadenylation (APA) can occur at more than half of all human genes, greatly enhancing the cellular repertoire of mRNA isoforms. As these isoforms can have altered stability, localisation and coding potential, deregulation of APA can disrupt gene expression and this has been linked to many diseases including cancer progression. How APA generates cancer-specific isoform profiles and what their physiological consequences are, however, is largely unclear.

Alternative cleavage and polyadenylation of genes associated with protein turnover and mitochondrial function are deregulated in Parkinson's, Alzheimer's and ALS disease.

Background: Transcriptome wide changes have been assessed extensively during the progression of neurodegenerative diseases. Alternative polyadenylation (APA) occurs in over 70% of human protein coding genes and it has recently been recognised as a critical regulator of gene expression during disease. However, the effect of APA in the context of neurodegenerative diseases, to date, has not been widely investigated.

Cleavage and polyadenylation: Ending the message expands gene regulation.

Cleavage and polyadenylation (pA) is a fundamental step that is required for the maturation of primary protein encoding transcripts into functional mRNAs that can be exported from the nucleus and translated in the cytoplasm. 3'end processing is dependent on the assembly of a multiprotein processing complex on the pA signals that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals, resulting in alternative cleavage and polyadenylation (APA), a widespread phenomenon that is important to establish cell state and cell type specific transcriptomes.

Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation.

Alternative cleavage and polyadenylation (APA) plays a crucial role in the regulation of gene expression across eukaryotes. Although APA is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we used a rigorous subcellular fractionation approach to compare APA profiles of cytoplasmic and nuclear RNA fractions from human cell lines.

Alternative polyadenylation: less than meets the eye?

With the advances in deep-sequencing techniques over the last decade, the study of alternative cleavage and polyadenylation (APA) has shifted from individual gene to whole transcriptome analysis. Findings from such global studies have elevated APA to its currently accepted status as a major player in the regulation of eukaryotic gene expression. Although ~70% of human genes have been shown to contain multiple cleavage and polyadenylation sites, the extent of the consequences of APA and its role in regulating physiological processes are still largely unknown.