A novel transcription initiation checkpoint--molecular mechanism by which RPAP2 negatively regulates transcription initiation

The team of Chen Xizi, Xu Yanhui and Chen Fei collaborated to discover and reveal a new transcription initiation checkpoint - the molecular mechanism by which RPAP2 negatively regulates transcription initiation

Gene transcription is a key link in the central dogma, using DNA as a template to generate RNA for protein synthesis

 PIC consists of RNA polymerase II ( Pol II ) and six universal transcription factors ( TFIIA, TFIIB, TFIIF, TFIIE and TFIIH )

On April 26 ,2022 , the team of Fudan University Chen Xizi, Xu Yanhui and Chen Fei collaborated in Cell ReportsThe journal publishes a research paper titled " RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex" online .

In the research of human Pol II complexes, the research team accidentally found that RPAP2 has a strong interaction with Pol II complexes when purifying human Pol II complexes.

 Since its identification, RPAP2 protein has been considered to be a phosphorylase involved in the transport of Pol II from the cytoplasm to the nucleus and has the function of removing the phosphorylation of Pol CTD .

The research team analyzed the structure of human RPAP2-Pol II (with an overall resolution of 2.

Using the rapid degradation system and high-throughput sequencing technology, the research team found that the deletion of RPAP2 in cells can lead to the accumulation of TFIIF and Pol II in the gene promoter region, resulting in the up-regulation of the overall gene expression level in cells, and this function is independent of RPAP2 phosphatase activity

Therefore, the researchers proposed that RPAP2 is a negative transcriptional regulator.

Figure 1.

This work proposes a brand-new transcription initiation checkpoint, revealing that RPAP2 acts as a "gatekeeper" to regulate the initiation of gene transcription, and provides a new idea for the study of the negative regulation mechanism of gene transcription

Doctoral student Wang Xinxin, doctoral student Qi Yilun, doctoral student Wang Zhenning, doctoral student Song Aixia and postdoctoral fellow of Fudan University Affiliated Cancer Hospital Wang Li are the co-first authors of this article