An essential signaling function of cytoplasmic NELFB is independent of RNA polymerase II pausing. J Biol Chem 2023 Nov;299(11):105259
Date
09/18/2023Pubmed ID
37717699Pubmed Central ID
PMC10591015DOI
10.1016/j.jbc.2023.105259Scopus ID
2-s2.0-85173908191 (requires institutional sign-in at Scopus site)Abstract
The four-subunit negative elongation factor (NELF) complex mediates RNA polymerase II (Pol II) pausing at promoter-proximal regions. Ablation of individual NELF subunits destabilizes the NELF complex and causes cell lethality, leading to the prevailing concept that NELF-mediated Pol II pausing is essential for cell proliferation. Using separation-of-function mutations, we show here that NELFB function in cell proliferation can be uncoupled from that in Pol II pausing. NELFB mutants sequestered in the cytoplasm and deprived of NELF nuclear function still support cell proliferation and part of the NELFB-dependent transcriptome. Mechanistically, cytoplasmic NELFB physically and functionally interacts with prosurvival signaling kinases, most notably phosphatidylinositol-3-kinase/AKT. Ectopic expression of membrane-tethered phosphatidylinositol-3-kinase/AKT partially bypasses the role of NELFB in cell proliferation, but not Pol II occupancy. Together, these data expand the current understanding of the physiological impact of Pol II pausing and underscore the multiplicity of the biological functions of individual NELF subunits.
Author List
Pan H, Cheng X, RodrÃguez PFG, Zhang X, Chung I, Jin VX, Li W, Hu Y, Li RAuthor
Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytoplasm
Mice
Phosphatidylinositols
Proto-Oncogene Proteins c-akt
RNA Polymerase II
Transcription, Genetic
