The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release.
EMBO Rep
; 24(3): e55699, 2023 03 06.
Article
em En
| MEDLINE
| ID: mdl-36629390
ABSTRACT
Release of promoter-proximally paused RNA Pol II into elongation is a tightly regulated and rate-limiting step in metazoan gene transcription. However, the biophysical mechanism underlying pause release remains unclear. Here, we demonstrate that the pausing and elongation regulator SPT5 undergoes phase transition during transcriptional pause release. SPT5 per se is prone to form clusters. The disordered domain in SPT5 is required for pause release and gene activation. During early elongation, the super elongation complex (SEC) induces SPT5 transition into elongation droplets. Depletion of SEC increases SPT5 pausing clusters. Furthermore, disease-associated SEC mutations impair phase properties of elongation droplets and transcription. Our study suggests that SEC-mediated SPT5 phase transition might be essential for pause release and early elongation and that aberrant phase properties could contribute to transcription abnormality in diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Polimerase II
/
Fatores de Elongação da Transcrição
Limite:
Animals
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China