Evidence map›Paper›PMID 42120422›Full record

ArticleNature communications2026

A tunable CTD grammar governs the spatial programming of the transcription cycle.

Qian Zhang, Haley A Hardtke, Yuanmin Zheng, Haopeng Yang, Alan Gerber, Mukesh Kumar Venkat Ramani, Edwin E Escobar, Jennifer S Brodbelt, Ruobo Zhou, Y Jessie Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Qian Zhang *Department of Molecular Biosciences, University of Texas, Austin, TX, USA.
Haley A Hardtke *Department of Molecular Biosciences, University of Texas, Austin, TX, USA.ORCID http://orcid.org/0000-0002-3718-5286
Yuanmin ZhengDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID http://orcid.org/0000-0001-6620-3634
Haopeng YangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Alan GerberAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3909-3606
Mukesh Kumar Venkat RamaniDepartment of Molecular Biosciences, University of Texas, Austin, TX, USA.
Edwin E EscobarDepartment of Chemistry, University of Texas, Austin, TX, USA.ORCID http://orcid.org/0000-0002-0086-6264
Jennifer S BrodbeltDepartment of Chemistry, University of Texas, Austin, TX, USA.
Ruobo ZhouDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID http://orcid.org/0000-0001-8628-0282
Y Jessie ZhangDepartment of Molecular Biosciences, University of Texas, Austin, TX, USA. jzhang@cm.utexas.edu.ORCID http://orcid.org/0000-0002-9360-5388

Funding

Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological MoleculesR35GM139658 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S. · 2021 to 2025
$2.9M
Elucidating the SCP4 pathway as a multi-catalytic signaling dependency in acute myeloid leukemiaR01CA281106 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Christopher Vakoc, Yan Jessie Zhang · 2023 to 2026
$2.9M
Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcriptionR35GM148356 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Yan Jessie Zhang · 2023 to 2026
$2.3M
Deciphering the functional role of actin-spectrin-based membrane skeleton in subcellular compartmentalization of signaling proteins and cell signal transductionR35GM142973 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ZHOU, RUOBO · 2021 to 2025
$2.2M
NCI NIH HHS R01 CA281106NIGMS NIH HHS R35 GM139658NIGMS NIH HHS R35 GM142973NIGMS NIH HHS R35 GM148356
6 · The paper itself

Abstract

RNA polymerase II transcribes all protein-coding genes in eukaryotes, with its C-terminal domain (CTD) acting as a regulatory platform throughout the transcription cycle. Despite its simple sequence, the conserved heptad repeats encode a regulatory grammar critical for transcription initiation, elongation, and termination. Using structural analysis, single-molecule imaging, and synthetic CTD-engineered Pol II constructs, we define the minimal sequence requirements across transcriptional stages. We show that while SP motifs are essential phosphorylation sites, flanking residues can tolerate variability. In contrast, the periodic positioning of tyrosine residues is indispensable for pre-initiation complex (PIC) formation through interactions with the Mediator, which are disrupted upon Ser5 phosphorylation, triggering promoter escape. This supports a model where sequential tyrosine engagement stabilizes PIC assembly, and progressive phosphorylation propels Pol II escape. Site-specific Ser2/5 phosphorylation orchestrates 3'-end processing factor recruitment. These findings define the functional grammar of the Pol II CTD and explain how a low-complexity sequence achieves regulatory specificity.

Indexed as

RNA Polymerase IITranscription, GeneticPhosphorylationPromoter Regions, GeneticProtein DomainsSaccharomyces cerevisiaeTyrosineRNA Polymerase IITyrosine

Identifiers

PMID42120422
PMCPMC13377220

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.