Community Research and Development Information Service - CORDIS

Unveiling transcription regulation

An important process following gene transcription entails removal of the non-coding sequences from the pre-messenger RNA (mRNA) molecules, a process known as splicing. A European study investigated the uncharted waters of mRNA splicing by focusing on the proteins governing the process.
Unveiling transcription regulation
Splicing is very often cell-dependent, leading to the expression of structurally and functionally distinct protein isoforms from a single gene. However, the splicing factors that are responsible for inclusion or exclusion of a particular exon remain to be determined.

In the EU-funded 'Coordinated regulation of transcription and pre-mRNA splicing at gene promoters' (PRE-MRNA SPLICING) proposal, scientists wished to identify the targets of an important family of splicing regulators, the SR proteins. These proteins ensure that the intron–exon boundaries are properly defined and recruit the spliceosome. These factors were depleted in vitro in order to determine their role in regulating transcriptional splicing.

Scientists subsequently performed RNA sequencing to find that the SR proteins had different gene regulatory potentials. Additionally, regulation of gene expression by these proteins was shown to be complex and can be observed both at the level of alternative splicing and total gene expression.

An additional line of work of the PRE-MRNA SPLICING project entailed the investigation of 5' end capping, a further modification of mRNAs required for both efficient splicing and translation. Scientists succeeded in determining for the first time the genome-wide localisation of a component of the nuclear cap binding complex CBP 20. By comparing the genomic distribution of this component with the RNA polymerase II and III occupancy, they hoped to gain insight into the regulation of gene expression at specific gene promoters.

Apart from providing fundamental knowledge into the role of SR proteins in regulating splicing and thus gene expression, the findings of the PRE-MRNA SPLICING study could have clinical applicability. Given that expression of some SR proteins is mis-regulated in cancer, the outcome of this work may serve as the basis for investigating the impact of abnormal regulation by SR proteins.

Related information

Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top