The origins and importance of spliceosomal introns comprise one of the longest-abiding mysteries of molecular evolution. Considerable debate remains over several aspects of the evolution of spliceosomal introns, including the timing of intron origin and proliferation, the mechanisms by which introns are lost and gained, and the forces that have shaped intron evolution. Recent important progress has been made in each of these areas. Patterns of intron-position correspondence between widely diverged eukaryotic species have provided insights into the origins of the vast differences in intron number between eukaryotic species, and studies of specific cases of intron loss and gain have led to progress in understanding the underlying molecular mechanisms and the forces that control intron evolution.
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http://dx.doi.org/10.1038/nrg1807 | DOI Listing |
Nat Commun
January 2025
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
The assembly of repressive heterochromatin in eukaryotic genomes is crucial for silencing lineage-inappropriate genes and repetitive DNA elements. Paradoxically, transcription of repetitive elements within constitutive heterochromatin domains is required for RNA-based mechanisms, such as the RNAi pathway, to target heterochromatin assembly proteins. However, the mechanism by which heterochromatic repeats are transcribed has been unclear.
View Article and Find Full Text PDFSci Rep
January 2025
Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
High mortality and low response rates in lung cancer patients call for novel therapeutic targets. Data mining of whole-genome genetic dependency screens suggest Cell Division Cycle 40 (CDC40) to be an essential protein for lung cancer cell survival. We characterized CDC40 knockdown effects in multiple lung cancer cell lines, revealing induced cell cycle defects that resulted in strong growth inhibition and activation of apoptosis.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, California, USA; Center for Molecular Biology of RNA, University of California, Santa Cruz, California, USA. Electronic address:
The spliceosome protein, SF3B1 associates with U2 snRNP during early spliceosome assembly for pre-mRNA splicing. Frequent somatic mutations in SF3B1 observed in cancer necessitates characterization of its role in identifying the branchpoint adenosine of introns. Remarkably, SF3B1 is the target of three distinct natural product drugs, each identified by their potent anti-tumor properties.
View Article and Find Full Text PDFBiogenesis of circular RNA usually involves a backsplicing reaction where the downstream donor site is ligated to the upstream acceptor site by the spliceosome. For this reaction to occur, it is hypothesized that these sites must be in proximity. Inverted repeat sequences, such as Alu elements, in the upstream and downstream introns are predicted to base-pair and represent one mechanism for inducing proximity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Plants use seasonal cold to time the transition to reproductive development. Short- and long-term cold exposure is registered via parallel transcriptional shutdown and Polycomb-dependent epigenetic silencing of the major flowering repressor locus (). The cold-induced antisense transcripts () determine the dynamics of transcriptional shutdown, but the thermosensory mechanisms are still unresolved.
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