The multisubunit eukaryotic exosome is an essential RNA processing and degradation machine. In its nuclear form, the exosome associates with the auxiliary factor Rrp6p, which participates in both RNA processing and degradation reactions. The crystal structure of Saccharomyces cerevisiae Rrp6p displays a conserved RNase D core with a flanking HRDC (helicase and RNase D C-terminal) domain in an unusual conformation shown to be important for the processing function of the enzyme. Complexes with AMP and UMP, the products of the RNA degradation process, reveal how the protein specifically recognizes ribonucleotides and their bases. Finally, in vivo mutational studies show the importance of the domain contacts for the processing function of Rrp6p and highlight fundamental differences between the protein and its prokaryotic RNase D counterparts.
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http://dx.doi.org/10.1073/pnas.0604731103 | DOI Listing |
CRISPR J
January 2025
Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Bacteria and archaea acquire resistance to genetic parasites by preferentially integrating short fragments of foreign DNA at one end of a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR). "Leader" DNA upstream of CRISPR loci regulates transcription and foreign DNA integration into the CRISPR. Here, we analyze 37,477 CRISPRs from 39,277 bacterial and 556 archaeal genomes to identify conserved sequence motifs in CRISPR leaders.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Key Laboratory of Medical Molecular Virology (Ministry of Education / National Health Commission / Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200033, China.
Sialic acids derived from colonic mucin glycans are crucial nutrients for enteric bacterial pathogens like . The uptake and utilization of sialic acid in depend on coordinated regulons, each activated by specific metabolites at the transcriptional level. However, the mechanisms enabling crosstalk among these regulatory circuits to synchronize gene expression remain poorly understood.
View Article and Find Full Text PDFCells
December 2024
Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan.
Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information.
View Article and Find Full Text PDFDevelopment
January 2025
Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over development: it is expressed at higher levels in the blastula compared to the gastrula suggesting a critical role prior to gastrulation. We find depletion of Nup107 affects the differentiation of the early germ layers leading to an expansion of the ectoderm at the expense of endoderm and mesoderm.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Meier-Gorlin syndrome (MGORS) is a rare autosomal inherited form of primordial dwarfism. Pathogenic variants in 13 genes involved in DNA replication initiation have been identified in this disease, but homozygous intronic variants have never been reported. Additionally, whether growth hormone (GH) treatment can increase the height of children with MGORS is unclear.
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