Regulation of RNA transcript elongation in metazoans and its relevance to disease

Nature Reviews Molecular Cell Biology, Published online: 30 July 2026; doi:10.1038/s41580-026-01003-wThis Review discusses how transcript elongation by RNA polymerase II is regulated and how obstacles such as nucleosomes are overcome. Also discussed are the roles of transcription surveillance machineries, which ensure mRNA integrity and suppress spurious transcription, and how elongation defects contribute to diseases.

dlvr.it

Tunable kinetic destabilization governs RNA polymerase passage through a DNA-bound transcription factor

Eukaryotic transcription factors recognize short motifs, creating abundant binding sites within gene bodies and potential collisions with elongating RNA polymerases, yet how such encounters are resolved remains unclear. Here, we use optical tweezers to monitor RNA polymerase transcription through DNA-bound Egr-1, a zinc-finger transcription factor. Using DNA-fluctuation suppression as a readout of polymerase arrival, we show that Egr-1 delays elongation in an orientation- and rNTP-dependent manner, whereas force measurements indicate that RNAP does not bypass the TF by mechanical eviction. Instead, RNAP destabilizes the Egr-1-DNA complex over a short, structured interaction zone, increasing TF dissociation non-monotonically with distance. Monte Carlo simulations incorporating these kinetic changes recapitulate passage-time distributions. CpG methylation shortens Egr-1 residence time and largely eliminates the TF-dependent delay, suggesting a role for gene-body methylation in reducing kinetic barriers to elongation. These results reveal DNA-bound TFs as tunable barriers that locally shape transcription elongation. ### Competing Interest Statement The authors have declared no competing interest. Israel Science Foundation, https://ror.org/04sazxf24

biorxiv.org

Optimising DNA origami assembly by reducing off-target interactions - Nature Communications

Off-target binding can result in kinetic traps reducing the efficiency of DNA origami assembly. Here, the authors develop a software tool to design scaffold & staples with chosen sequences to avoi...

nature.com

Chromatin mechanics and regulatory protein function: insights from single-molecule force spectroscopy

Single-molecule force spectroscopy probes chromatin mechanics by resolving force-induced conformational transitions across multiple length scales. Rec…

sciencedirect.com

Chromatin mechanics and regulatory protein function: insights from single-molecule force spectroscopy

Single-molecule force spectroscopy probes chromatin mechanics by resolving force-induced conformational transitions across multiple length scales. Rec…

sciencedirect.com

Engineering a Mechanoresponsive DNA Origami Capsule for Drug Delivery to Narrowed Arteries

Since their inception, DNA origami nanostructures (DONs) have attracted great interest for their programmable geometry, nanoscale precision, and biocompatibility. Here, we present mechanoresponsive DO...

pubs.acs.org

Engineering a Mechanoresponsive DNA Origami Capsule for Drug Delivery to Narrowed Arteries

Since their inception, DNA origami nanostructures (DONs) have attracted great interest for their programmable geometry, nanoscale precision, and biocompatibility. Here, we present mechanoresponsive DO...

pubs.acs.org

Recent discoveries on the acquisition of the highest levels of human performance

Scientists have long debated the origins of exceptional human achievements. This literature review summarizes recent evidence from multiple domains on the acquisition of world-class performance. We re...

science.org

The White House Vision for Dismantling Science in One Simple Plot

Proposed NIH, NSF, and NASA budgets would be catastrophic for innovation and discovery. But they aren’t reality yet. The time to speak up is now.

open.substack.com

‘Scienticide’ in Argentina sparks huge protest by researchers

Hundreds of activists wearing gas masks took to the streets to call out their government for slashing science funding.

nature.com

Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis - Nature Communications

The authors establish the ChIP-CryoEM method, which combines chromatin immunopurification coupled with cryo-electron microscopy, to visualize native human RNAPII elongation complexes in action, with a...

nature.com

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

biorxiv.org

Direct observation of conformational dynamics of intrinsically disordered proteins at the single-molecule level

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) are integral to many biological processes, including neurotransmitter regulation, microtubule regulat...

biorxiv.org

Conservation of regulatory elements with highly diverged sequences across large evolutionary distances

Nature Genetics - Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence...

rdcu.be

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

biorxiv.org

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription

Transcription inhibitors also disrupt nuclear export. Here, Williams et al. reveal that mRNA export factors sense transcription inhibition and adapt by storing mature export-competent mRNA in nuclear speckles. This enables rapid release when transcription resumes and ensures retention of cellular identity and viability during a transient global transcription insult.

cell.com

Congratulations to Prof. Nabieh Ayoub on receiving the Award for Outstanding Excellence in Teaching for the Spring Semester of 2024 - פקולטה לביולוגיה Biology Faculty

The Faculty of Biology commends Prof. Ayoub for his significant contributions to teaching, his dedication to students, and his academic excellence. This recognition reflects his deep commitment to adv...

biology.technion.ac.il

ATAC and SAGA histone acetyltransferase modules facilitate transcription factor binding to nucleosomes independent of their acetylation activity

Abstract. Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recr

academic.oup.com

Best practice mass photometry: A guide to optimal single molecule mass measurement https://www.biorxiv.org/content/10.1101/2024.12.03.624087v1

Mass photometry (MP) has emerged as a powerful approach to study biomolecular structure, dynamics an

biorxiv.org

Controlling Transcription Elongation and Termination: More Than a Means to An End

sciencedirect.com

Single-molecule states link transcription factor binding to gene expression - Nature

A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor bind...

nature.com