# Regulation of myogenic transcription by the Paf1C complex

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $417,708

## Abstract

Usage of alternative cleavage and polyadenylation sites (APA) is emerging as a critical gene regulatory
mechanism, and it is known to play important roles in proliferation and development. Recent studies have
shown that 3’ untranslated region (UTR) lengthening occurs during mammalian embryonic development and
skeletal muscle differentiation. Lengthening occurs through alternative polyadenylation, although the
mechanisms that regulate this process are not completely understood. Furthermore, the mechanisms that link
cleavage and polyadenylation to RNA polymerase II (PolII) termination are not well understood. We have
investigated the basis for these key transcriptional mechanisms by focusing on the PAF complex (Paf1C) in
mammalian muscle cells. Paf1C acts as a platform to orchestrate a multitude of activities during the
transcription cycle, from transcriptional elongation to 3’ end processing. Our combined studies have revealed
novel roles for Paf1C in suppression of alternate polyadenylation (pA) sites as well as upstream and intragenic
antisense transcription. This proposal will leverage the complementary expertise of investigators who will use a
combination of state-of-the-art genomics, computational biology, and biochemistry to rigorously investigate the
role of the Paf1C complex in transcript processing and alternative polyadenylation, testing the role of these
critical events in myogenic differentiation. In two aims, we will explore potential physical and functional
connections between Paf1C and 3’ end processing factors, chromatin modifications, PolII progression, and
regulation of pA usage, and we will place their coordinated activities in the context of myogenic differentiation.
We will determine how Paf1C suppresses upstream anti-sense transcription and proximal pA usage,
investigating potential involvement of cleavage and polyadenylation factors. Lastly, we will determine whether
Paf1C serves a surveillance function by suppressing intergenic and intragenic transcription through
interactions with another elongation factor. Altogether, these studies will attempt to integrate diverse roles for
Paf1C in chromatin modifications with regulation of alternative polyadenylation, readthrough and antisense
transcription, and changes in gene expression underlying myogenic differentiation. More broadly, our studies
will reveal roles for Paf1C in genome surveillance that regulate production of lncRNAs and suppression of
antisense transcription. Our studies are relevant to human health because loss of function mutations in a
Paf1C component lead to parathyroid tumors, and mutations in a cleavage and polyadenylation factor lead to a
type of muscular dystrophy. Thus, our proposal will contribute fundamental new insights into basic
transcriptional mechanisms as well as potentially important information regarding human disease.

## Key facts

- **NIH application ID:** 9984480
- **Project number:** 5R01GM122395-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Brian D Dynlacht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,708
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984480

## Citation

> US National Institutes of Health, RePORTER application 9984480, Regulation of myogenic transcription by the Paf1C complex (5R01GM122395-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9984480. Licensed CC0.

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