ArticleNature structural & molecular biology2024
Transcription directionality is licensed by Integrator at active human promoters.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- Adulthood depletion of Integrator extends lifespan and healthspan via defective pre-mRNA processing.bioRxiv : the preprint server for biology · 2026Article
- Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metamorphosis and lncRNAs: A Close Relationship.Genesis (New York, N.Y. : 2000) · 2026Review
- Coordinating mRNA maturation: The U1 relay model.Molecular cell · 2026Review
- RNA G-quadruplexes promote codon repeat-associated ribosomal frameshifting in human genes.Nucleic acids research · 2026Article
- Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis.Cell reports · 2025Article
- Dual roles of DEAD-box RNA helicase Brr2 in genome stability regulation.Nature communications · 2025Article
- Integrator promotes the association of TFIID and RNA polymerase II to maintain pluripotency during development.Molecular cell · 2025Article
- Restrictor slows RNAPII elongation to promote termination at noncoding RNA loci.Genes & development · 2025Article
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Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A universal characteristic of eukaryotic transcription is that the promoter recruits RNA polymerase II (RNAPII) to produce both precursor mRNAs (pre-mRNAs) and short unstable promoter upstream transcripts (PROMPTs) toward the opposite direction. However, how the transcription machinery selects the correct direction to produce pre-mRNAs is largely unknown. Here, through multiple acute auxin-inducible degradation systems, we show that rapid depletion of an RNAPII-binding protein complex, Integrator, results in robust PROMPT accumulation throughout the genome. Interestingly, the accumulation of PROMPTs is compensated by the reduction of pre-mRNA transcripts in actively transcribed genes. Consistently, Integrator depletion alters the distribution of polymerase between the sense and antisense directions, which is marked by increased RNAPII-carboxy-terminal domain Tyr1 phosphorylation at PROMPT regions and a reduced Ser2 phosphorylation level at transcription start sites. Mechanistically, the endonuclease activity of Integrator is critical to suppress PROMPT production. Furthermore, our data indicate that the presence of U1 binding sites on nascent transcripts could counteract the cleavage activity of Integrator. In this process, the absence of robust U1 signal at most PROMPTs allows Integrator to suppress the antisense transcription and shift the transcriptional balance in favor of the sense direction.
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Registered trials
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.