Topic
Exon
About: Exon is a research topic. Over the lifetime, 38308 publications have been published within this topic receiving 1745408 citations. The topic is also known as: exons.
Papers published on a yearly basis
Papers
More filters
TL;DR: It is reported that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.
Abstract: Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life1, yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus, forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound significantly more weakly to DNA. R-loop formation results in transcriptional pausing, which has been shown to coincide with splicing factor recruitment and AS2-4. This report presents a novel mechanistic insight for how at least a subset of circRNAs probably contribute to increased splicing efficiency of their cognate exon-skipped messenger RNA and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.
386 citations
TL;DR: The human mutY gene (hMYH) is cloned from both genomic and cDNA libraries and provides an important function in the repair of oxidative damage to DNA and helps to prevent mutations from oxidative lesions.
Abstract: We have cloned the human mutY gene (hMYH) from both genomic and cDNA libraries. The human gene contains 15 introns and is 7.1 kb long. The 16 exons encode a protein of 535 amino acids that displays 41% identity to the Escherichia coli protein, which provides an important function in the repair of oxidative damage to DNA and helps to prevent mutations from oxidative lesions. The human mutY gene maps on the short arm of chromosome 1, between p32.1 and p34.3.
386 citations
TL;DR: Two cDNAs are identified which predict distinct peptide precursors of 153 and 195 amino acids, confirming the hypothesis that at least two IGF-I mRNAs are generated by alternative RNA processing of the primary gene transcript.
386 citations
TL;DR: In this article, specific antibodies were prepared that identified the gene product of BRCA2 as a 390-kDa nuclear protein, and direct binding of human RAD51 to each of the four single 30-amino acid BRC repeats located at the 5′ portion of exon 11 of bRCa2 was demonstrated.
Abstract: The BRCA2 gene was identified based on its involvement in familial breast cancer. The analysis of its sequence predicts that the gene encodes a protein with 3,418 amino acids but provides very few clues pointing to its biological function. In an attempt to address this question, specific antibodies were prepared that identified the gene product of BRCA2 as a 390-kDa nuclear protein. Furthermore, direct binding of human RAD51 to each of the four single 30-amino acid BRC repeats located at the 5′ portion of exon 11 of BRCA2 was demonstrated. Such an interaction is significant, as BRCA2 and RAD51 can be reciprocally coimmunoprecipitated by each of the individual, specific antibodies and form complexes in vivo. Inferring from the function of RAD51 in DNA repair, human pancreatic cancer cells, Capan-1, expressing truncated BRCA2 were shown to be hypersensitive to methyl methanesulfonate (MMS) treatment. Exogenous expression of wild-type BRCA2, but not BRC-deleted mutants, in Capan-1 cells confers resistance to MMS treatment. These results suggest that the interaction between the BRC repeats of BRCA2 and RAD51 is critical for cellular response to DNA damage caused by MMS.
385 citations
TL;DR: An initial characterization of the human VDR gene and its promoter is reported, suggesting a molecular mechanism for the previously observed ability of retinoic acid to induce the VDR.
Abstract: The vitamin D receptor (VDR) is known to mediate the pleiotropic biological actions of 1,25-dihydroxyvitamin D3 through its ability to modulate the expression of target genes. The regulation of this ligand-activated cellular transcription factor is reported to occur at both transcriptional and posttranslational levels. To begin to address the molecular basis by which the VDR gene is regulated transcriptionally, we report here an initial characterization of the human VDR gene and its promoter. We isolated several overlapping λ-phage and cosmid clones that cover more than 100 kb of human DNA and contained the entire VDR gene. The gene is comprised of 11 exons that, together with intervening introns, span approximately 75 kb. The noncoding 5′-end of the gene includes exons 1A, 1B, and 1C. Eight additional exons (exons 2–9) encode the structural portion of the VDR gene product. While primer extension and S1 nuclease-mapping studies reveal several common transcriptional start sites, three unique mRNA species a...
385 citations