Understanding the transcriptional landscape of non-coding genome in mammals

Abstract

Widespread transcription in mammals revealed unexpected discovery of non-coding elements like long noncoding RNAs (lncRNAs) and repetitive elements. First, lncRNAs were previously identified in limited number of tissues or cell lines in mouse and the discovery of lncRNAs was still pending in many other tissues in mouse. To address this, we applied a computational pipeline that discovered 2,803 highconfidence novel lncRNAs by mapping and de novo assembling billions of RNA-Seq reads in eight tissues and a primary cell line in mouse. Further, we integrated this catalog of lncRNAs with chromatin state maps and found many regulatory lncRNAs (promoter-associated and enhancer-associated lncRNAs). Second, more than half of the human genome contains repetitive elements. However, it is not clear how they are expressed across all mammalian tissues. To address this, as a part of Genotype- Tissue Expression (GTEx) project, we profiled repetitive elements using 8,551 poly-A RNA-Seq datasets from 53 tissues across 550 individuals and found various repeat families transcribed across multiple human tissues in a tissue-specific manner. In summary, to understand the transcriptional landscape of non-coding genome, we mainly analyzed RNA-Seq datasets across many tissues in mammals and show that the non-coding elements like lncRNA and repetitive elements are not only transcribed but also tissue-specific. Together, this thesis work defines a unique collection of non-coding elements that are transcribed and tissue-specific in mammalian tissues.Una gran parte del genoma de mamiefores se expresa en forma de ARNs y se conoce hoy en dia que una gran parte de estos transcritos son no codificantes llamados lncRNAs y que contienen elementos repetitivos. En ratones, estos han sido identificados recientemente en un número limitado de tejidos y líneas celulares. Esta tesis presenta un trabajo exhaustivo de estudio de lnRNAs en ratón en ocho tejidos y una línea celular. En este trabajo se descubrieron 2803 nuevos lncRNAs a los cuáles se les asignó una función reguladora (asociados a promotores o activadores “enhancers”) en el genoma usando datos del estado de la cromatina. Asimismo, más de la mitad del genoma humano contiene elementos repetitivos. Desafortunadamente no se conoce el patrón de expresión de estos elementos repetitivos en los tejidos mamíferos. Como miembros del proyecto GTEx (GenotypeviTissue Expression), analizamos la expresión de estos elementos repetitivos en 8,551 muestras de polyA RNA-Seq en 53 tejidos de 550 individuos. Encontramos que muchas familias de elementos repetitivos son expresadas en tejidos específicos en varios individuos, y representan una característica peculiar de la identidad de cada tejido en humanos.Programa de doctorat en Biomedicina