Dynamic interaction between tentacle-tethered microdomains in Integrator and NELF regulates the promoter-proximal pause checkpoint

Authors

Blears, D., Bech, P., Martinez, D. L., Dai, P., Shah, R. A., Fong, N., Han, Z., Mitter, R., Sheridan, R., Johansen, J. V., Dirac-Svejstrup, A. B., Bentley, D., Svejstrup, J. Q.

Abstract

Negative Elongation Factor (NELF) and Integrator are general regulators of transcriptional pausing and premature termination at the beginning of protein-coding genes. While NELF is a key pausing factor, Integrator triggers premature termination of dysfunctional RNAPII complexes. Here, we identify a direct interaction between the plant homeodomain (PHD) finger of Integrator subunit 12 (INTS12) and a previously unrecognized C-terminal domain (CTD) in the flexible tentacle of NELF-A. Mutation of either domain disrupts the interaction, and although RNAPII-associated pausing complexes still form, they are dysfunctional. Importantly, while deletion of the INTS12 PHD finger functionally mimics Integrator loss, a single point mutation in NELF-A CTD instead mimics loss of NELF, suggesting the presence of competitive interactions. Together, our findings uncover a novel mode of PHD finger binding and outline how an interaction between Integrator and NELF regulates transcriptional pausing and premature termination.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 10 Jul 2026.

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