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cis and trans-acting mechanisms of lincRNA function

English title cis and trans-acting mechanisms of lincRNA function
Applicant Marques Ana
Number 179065
Funding scheme SNSF Professorships
Research institution Département de biologie computationnelle Faculté de biologie et de médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Molecular Biology
Start/End 01.10.2018 - 30.09.2020
Approved amount 744'301.00
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All Disciplines (2)

Discipline
Molecular Biology
Genetics

Keywords (4)

noncoding RNAs; regulation of gene expression; genomics; lincRNAs

Lay Summary (French)

Lead
Les ARN non codants contribuent à divers processus biologiques chez l'homme, y compris la maladie. Cependant, moins de 1% des ARN non codants actuellement annotés dans le génome humain ont une fonction établie. Combler le fossé entre la découverte et l'attribution de fonction a des lncRNA est l'un des plus grands défis en biologie.
Lay summary

Le génome d'un individu contient les instructions (les gènes) nécessaires à son développement, son maintien et sa survie. L’expression des gènes en ARN permet la production de la plupart des molécules essentielles à la différenciation et à la viabilité des toutes cellules qui composent un organisme multicellulaire complexe, tel que l'homme. Comprendre les processus que contrôlent l’expression des gènes est essentiel pour établir comment l'information contenue dans le génome détermine le développement et la survie de l'organisme.

L'avènement de nouvelles technologies, telles que le séquençage de nouvelle génération, a révélé que plus des deux tiers des gènes dans le génome humain ne code pas pour des protéines. Malgré leur prévalence, les fonctions précises et la pertinence biologique de la grande majorité des ARN non codants restent largement inconnues. Notre recherche vise à comprendre les contributions de ARN non codant qui sont plus longs que 200 nucléotides (longs ARN non codants, lncRNA).

Les lncRNA contribuent à divers processus biologiques chez l'homme, y compris la maladie. Cependant, moins de 1% des 16 000 lncRNA actuellement annotés dans le génome humain ont une fonction établie. Combler le fossé entre la découverte et l'attribution de fonction a des lncRNA est l'un des plus grands défis en biologie.

Les lncRNA régulent l'expression des gènes à travers une variété de mécanismes, mais la connaissance actuelle du code sous-jacent à ces fonctions lncRNA est limitée. Notre recherche vise à établir le code des fonctions de l'lncRNA et à définir les caractéristiques les motifs qui determinent leurs fonctions. Cela facilitera la prédiction des fonctions des lncRNAs et guidera le travail expérimental pour évaluer leurs rôles biologiques permettant finalement d'établir comment les lncRNA contribuent au contrôle de l'expression des gènes et comment leur perturbation conduit à la maladie

Direct link to Lay Summary Last update: 09.07.2018

Responsible applicant and co-applicants

Employees

Publications

Publication
The activity of human enhancers is modulated by the splicing of their associated lncRNAs
TanJennifer, MarquesAna Claudia (2020), The activity of human enhancers is modulated by the splicing of their associated lncRNAs, in Biorxiv, NA.
A Protocol for Transcriptome-Wide Inference of RNA Metabolic Rates in Mouse Embryonic Stem Cells
(2020), A Protocol for Transcriptome-Wide Inference of RNA Metabolic Rates in Mouse Embryonic Stem Cells, in Frontiers in Genetics, NA.
Estimating RNA dynamics using one time point for one sample in a single-pulse metabolic experiment
(2020), Estimating RNA dynamics using one time point for one sample in a single-pulse metabolic experiment, in Biorxiv, NA.
Loss-of-function of the long non- coding RNA A830019P07Rik in mice does not affect insulin expression and secretion
(2020), Loss-of-function of the long non- coding RNA A830019P07Rik in mice does not affect insulin expression and secretion, in Scientific Reports, 10:6413.
Splicing of enhancer-associated lincRNAs contributes to enhancer activity
Tan Jennifer Y, Biasini Adriano, Young Robert S, Marques Ana C (2020), Splicing of enhancer-associated lincRNAs contributes to enhancer activity, in Life Science Alliance, e202000663.
Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
Buendía Gustavo A. Ruiz, Leleu Marion, Marzetta Flavia, Vanzan Ludovica, Tan Jennifer Y., Ythier Victor, Randall Emma L., Marques Ana C., Baubec Tuncay, Murr Rabih, Xenarios Ioannis, Dion Vincent (2020), Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion, in Science Advances, eaaz4012.
Translation is required for miRNA-dependent decay of endogenous transcripts
(2020), Translation is required for miRNA-dependent decay of endogenous transcripts, in Biorxiv, NA.
LincRNA sequences are biased to counteract their translation
(2019), LincRNA sequences are biased to counteract their translation, in Biorvix, NA.
The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance
Biasini Adriano, Smith Adam Alexander Thil, Abdulkarim Baroj, Tan Jennifer Yihong, da Silva Maria Ferreira, Marques Ana (2019), The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance, in iScience, 101291.
The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor
Coe Elizabeth A., Widlund Hans, Tan Jennifer Y., Shapiro Michael, Louphrasitthiphol Pakavarin, Bassett Andrew R., Marques Ana C., Goding Colin R., Vance Keith W. (2019), The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor, in PLoS Genetics, e1008501.
TIP5 safeguards genome architecture of ground-state pluripotent stem cells
(2019), TIP5 safeguards genome architecture of ground-state pluripotent stem cells, in Biorxiv, NA.

Datasets

4sU metabolic labeled transcripts in mESCs

Author Biasini, Adriano
Persistent Identifier (PID) GSE111951
Repository GEO


Associated projects

Number Title Start Funding scheme
150667 Mechanisms of long intergenic noncoding RNAs in homeostasis and disease 01.10.2014 SNSF Professorships
150667 Mechanisms of long intergenic noncoding RNAs in homeostasis and disease 01.10.2014 SNSF Professorships

Abstract

Although long intergenic noncoding RNAs (lincRNAs) contribute to diverse aspects of mammalian biology, those with established functions account for fewer than 1% of all annotated lincRNAs. Bridging the gap between discovery and functional assignment of noncoding RNAs is one of the greatest challenges in Biology. Individual lincRNAs regulate gene expression in a variety of ways. This molecular heterogeneity has hindered attempts to develop prediction methods that leverage the insights gained, through genetics, on individual lincRNAs. Nonetheless, the properties and motifs that underlie a limited number of lincRNA molecular mechanisms of function are partially known. Focusing on lincRNAs associated with these molecular functions and establishing in detail their prevalence, distinctive features and mechanisms of function will accelerate our understanding of what is the biological relevance of gene expression regulation by lincRNAs. I propose to determine the distinguishing features and underlying molecular mechanisms of two prevalent and disease-relevant molecular classes of lincRNAs: 1) lincRNAs with microRNA-dependent functions and 2) enhancer associated lincRNAs.The information gained on these two lincRNA classes will facilitate the development of tools to allow their robust genome wide identification and guide experimental work to assess their biological roles.
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