The Nrd1-Nab3-Sen1 (NNS) complex pathway is responsible for transcription termination of cryptic unstable transcripts and sn/snoRNAs. The NNS complex recognizes short motifs on the nascent RNA, but the presence of these sequences alone is not sufficient to define a functional terminator. We generated a homogeneous set of several hundreds of artificial, NNS-dependent terminators with an in vivo selection approach. Analysis of these terminators revealed novel and extended sequence determinants for transcription termination and NNS complex binding as well as supermotifs that are critical for termination. Biochemical and structural data revealed that affinity and specificity of RNA recognition by Nab3p relies on induced fit recognition implicating an α-helical extension of the RNA recognition motif. Interestingly, the same motifs can be recognized by the NNS or the mRNA termination complex depending on their position relative to the start of transcription, suggesting that they function as general transcriptional insulators to prevent interference between the non-coding and the coding yeast transcriptomes.
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http://dx.doi.org/10.1038/emboj.2012.237 | DOI Listing |
Cell Rep
January 2025
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.
View Article and Find Full Text PDFFASEB J
January 2025
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions.
View Article and Find Full Text PDFPlant Genome
March 2025
School of Biological and Behavioural Sciences, Queen Mary University of London, London, E1 4NS, UK.
Repetitive DNA contributes significantly to plant genome size, adaptation, and evolution. However, little is understood about the transcription of repeats. This is addressed here in the plant green foxtail millet (Setaria viridis).
View Article and Find Full Text PDFGenome Biol
January 2025
College of Agriculture & Biotechnology, Zhejiang University, Hangzhou, 310058, China.
Background: Fruit acidity and color are important quality attributes in peaches. Although there are some exceptions, blood-fleshed peaches typically have a sour taste. However, little is known about the genetic variations linking organic acid and color regulation in peaches.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Structural Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Many bacteriophages modulate host transcription to favor expression of their own genomes. Phage satellite P4 polarity suppression protein, Psu, a building block of the viral capsid, inhibits hexameric transcription termination factor, ρ, by presently unknown mechanisms. Our cryogenic electron microscopy structures of ρ-Psu complexes show that Psu dimers clamp two inactive, open ρ rings and promote their expansion to higher-oligomeric states.
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