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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Structural, Functional and Evolutionary Characterization of Sense-Antisense Transcripts in Mammals

Dickens, Charles 2009 May 1900 (has links)
Sense-antisense transcripts (SATs) are messenger RNA (mRNA) transcripts that have regions that are complementary to regions of other mRNA transcripts. SATs may play an influential role in the regulation of gene expression. One evolutionary event that has had a dramatic impact on many genomes is the widespread dispersal of repetitive sequences which includes transposable elements (TEs) as well as simple and tandem repeats. Approximately 45% of the human and 37.5% of the mouse genomes are composed of repeats derived from transposable elements. A group of SATs was identified as resulting from transposable elements integrating into the coding strand of some genes and into the template strand of the coding region of other genes. These SATs may add to the complexity of an organism's regulatory network or they may be the result of rather recent TE activities yet to succumb to sequence divergence. The human, mouse and bovine genomes were analyzed for SATs using publicly available datasets and bioinformatics analysis tools. Each sense-antisense binding region (SABR) was aligned to transposable elements from the RepBase repeat database revealing many SABRs containing TE sequence in a large portion of the sequence. A Gene Ontology analysis on subsets of the data showed enrichments for the functional category of "DNA repair" and the component category "cytoplasm". An analysis of the substitution rates in human and mouse across the 3' UTRs of transcripts containing SABRs at the 5' end of their 3' UTRs showed that the substitution rate in the region of the SABR was lower than compared to the beginning of the 3' UTR. The lower percent GC composition found at the 3' end of the 3' UTRs could be attributed to conserved poly-A signals in this region.
2

Cytoplasmic control of sense-antisense mRNA pairs in Saccharomyces cerevisiae / Contrôle cytoplasmique des paires d'ARN messager sens-antisens chez Saccharomyces cerevisiae

Navickas, Albertas 23 September 2016 (has links)
Les récentes études transcriptomiques chez divers organismes ont montré que la transcription des gènes convergents peut produire des ARN messagers (ARNm) chevauchants. Ce phénomène a été analysé dans le contexte de l’interférence par ARN (ARNi) nucléaire, et peu d’information existe quant au destin cytoplasmique des messagers 3’ chevauchants ou leur impact sur l’expression des gènes. Dans ce travail, nous avons abordé les conséquences potentielles de l’interaction entre des paires d’ARNm sens-antisens chez Saccharomyces cerevisiae, un organisme modèle naturellement dépourvu de l’ARNi. Nous avons démontré que les extrémités 3’ complémentaires des ARNm peuvent interagir dans le cytoplasme et moduler la stabilité ainsi que la traduction d’ARNm. Nos résultats sont issus d’une étude détaillée d’une paire d’ARNm convergents, POR1 et OCA2, ensuite généralisée par l’approche de l’ARNi reconstituée chez S. cerevisiae. L’analyse globale a confirmé que dans les cellules sauvages, les paires d’ARNm sens-antisens forment des duplexes d’ARN in vivo et ont un rôle potentiel à moduler l’expression d’ARNm ou de protéines respectifs, dans des différentes conditions de croissance. Nous avons montré que le destin de centaines des messagers convergents est contrôlé par Xrn1, révélant l’importance de cette exoribonucléase 5’-3’ cytoplasmique très conservée dans la régulation post-transcriptionnelle des gènes convergents. Notre travail ouvre donc la perspective de considérer un nouveau mécanisme de l’interaction entre les paires d’ARNm sens-antisens dans le cytoplasme, chez les organismes contenant ou non la voie de l’interférence par ARN. / Recent transcriptome analyses have revealed that convergent gene transcription can produce many 3’ overlapping mRNAs in diverse organisms. This phenomenon has been studied in the context of nuclear RNA interference (RNAi) pathway, however little is known about the cytoplasmic fate of 3’ overlapping messengers or their impact on gene expression. In this work, we address the outcomes of interaction between sense-antisense mRNA pairs in Saccharomyces cerevisiae, a model organism naturally devoid of RNAi. We demonstrate that the complementary tails of 3’ overlapping mRNAs can interact in the cytoplasm in a sequence-specific manner and promote post-transcriptional remodeling of mRNA stability and translation. Our findings are based on the detailed analysis of a convergent mRNA pair, POR1 and OCA2, subsequently generalized using the reconstituted RNAi approach in S. cerevisiae. Genome-wide experiments confirm that in wild-type cells, sense-antisense mRNA pairs form RNA duplexes in vivo and thus have potential roles in modulating the respective mRNA or protein levels under different growth conditions. We show that the fate of hundreds of messenger-interacting messengers is controlled by Xrn1, revealing the extent to which this conserved 5’-3’ cytoplasmic exoribonuclease plays an unexpected but key role in the post-transcriptional control of convergent gene expression. In sum, our work opens a perspective to consider an additional, cytoplasmic mechanism of interaction between sense-antisense mRNA pairs, in both RNAi-positive and negative organisms.

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