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Updated: May 7, 2026

Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on (TRO) Approach
Published on: March 12, 2017
Human snRNA genes use polyadenylation factors to promote efficient transcription termination
Dawn O'Reilly1, Olga V Kuznetsova, Clelia Laitem
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK and CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3PT, UK.
Abstract:
RNA polymerase II transcribes both protein coding and non-coding RNA genes and, in yeast, different mechanisms terminate transcription of the two gene types. Transcription termination of mRNA genes is intricately coupled to cleavage and polyadenylation, whereas transcription of small nucleolar (sno)/small nuclear (sn)RNA genes is terminated by the RNA-binding proteins Nrd1, Nab3 and Sen1. The existence of an Nrd1-like pathway in humans has not yet been demonstrated. Using the U1 and U2 genes as models, we show that human snRNA genes are more similar to mRNA genes than yeast snRNA genes with respect to termination. The Integrator complex substitutes for the mRNA cleavage and polyadenylation specificity factor complex to promote cleavage and couple snRNA 3'-end processing with termination. Moreover, members of the associated with Pta1 (APT) and cleavage factor I/II complexes function as transcription terminators for human snRNA genes with little, if any, role in snRNA 3'-end processing. The gene-specific factor, proximal sequence element-binding transcription factor (PTF), helps clear the U1 and U2 genes of nucleosomes, which provides an easy passage for pol II, and the negative elongation factor facilitates termination at the end of the genes where nucleosome levels increase. Thus, human snRNA genes may use chromatin structure as an additional mechanism to promote efficient transcription termination in vivo.
Insights
Human small nuclear RNA (snRNA) gene transcription termination differs from yeast, utilizing the Integrator complex and APT/CF I/II factors. Chromatin structure also aids termination for U1 and U2 genes.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Processing
Background:
- RNA polymerase II transcribes protein-coding and non-coding RNAs.
- Yeast employs distinct termination mechanisms for mRNA and small nucleolar/nuclear (sno/sn)RNA genes.
- Human sno/snRNA termination pathways remain largely uncharacterized.
Purpose of the Study:
- To investigate the mechanisms of human snRNA gene transcription termination.
- To compare human snRNA termination with yeast and mRNA termination pathways.
- To identify factors involved in human snRNA 3'-end processing and termination.
Main Methods:
- Utilized U1 and U2 snRNA genes as model systems.
- Investigated the roles of the Integrator complex, APT, and cleavage factor I/II complexes.
- Examined the influence of proximal sequence element-binding transcription factor (PTF) and negative elongation factor.
Main Results:
- Human snRNA termination shares similarities with mRNA termination, unlike in yeast.
- The Integrator complex couples snRNA 3'-end processing with termination.
- APT and cleavage factor I/II complexes act as terminators for human snRNA genes.
- PTF and negative elongation factor, along with chromatin structure, facilitate termination.
Conclusions:
- Human snRNA genes employ a termination mechanism more akin to mRNA genes.
- The Integrator complex plays a crucial role in coupling processing and termination.
- Chromatin structure may serve as an additional regulatory mechanism for efficient termination in vivo.
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