0000000000761694
AUTHOR
Enrique M. Muro
showing 7 related works from this author
Comprehensive translational control of tyrosine kinase expression by upstream open reading frames
2016
Post-transcriptional control has emerged as a major regulatory event in gene expression and often occurs at the level of translation initiation. Although overexpression or constitutive activation of tyrosine kinases (TKs) through gene amplification, translocation or mutation are well-characterized oncogenic events, current knowledge about translational mechanisms of TK activation is scarce. Here, we report the presence of translational cis-regulatory upstream open reading frames (uORFs) in the majority of transcript leader sequences of human TK mRNAs. Genetic ablation of uORF initiation codons in TK transcripts resulted in enhanced translation of the associated downstream main protein-codin…
Identification of transcribed protein coding sequence remnants within lincRNAs
2018
Abstract Long intergenic non-coding RNAs (lincRNAs) are non-coding transcripts >200 nucleotides long that do not overlap protein-coding sequences. Importantly, such elements are known to be tissue-specifically expressed and to play a widespread role in gene regulation across thousands of genomic loci. However, very little is known of the mechanisms for the evolutionary biogenesis of these RNA elements, especially given their poor conservation across species. It has been proposed that lincRNAs might arise from pseudogenes. To test this systematically, we developed a novel method that searches for remnants of protein-coding sequences within lincRNA transcripts; the hypothesis is that we can t…
RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease
2020
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD ca…
The distributions of protein coding genes within chromatin domains in relation to human disease.
2019
Abstract Background Our understanding of the nuclear chromatin structure has increased hugely during the last years mainly as a consequence of the advances in chromatin conformation capture methods like Hi-C. The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled. Resul…
A Methodology to Study Pseudogenized lincRNAs
2021
Long intergenic noncoding RNAs (lincRNAs) are known to be tissue specifically expressed and able to regulate functional protein-coding genes: some can even act as competing endogenous RNAs (ceRNAs), because microRNAs can bind to them instead of the corresponding mRNA binding sites. Some lincRNAs contain remnants of protein-coding sequences and it has been hypothesized that they might arise after a pseudogenization processes. However, a major limitation in the study of such phenomenon is the lack of proper computational tools designed to align/analyze protein-coding sequences and noncoding sequences. To overcome this limitation, we published a method that finds the remnants of protein-coding…
DiseaseLinc: Disease Enrichment Analysis of Sets of Differentially Expressed LincRNAs
2021
Long intergenic non-coding RNAs (LincRNAs) are long RNAs that do not encode proteins. Functional evidence is lacking for most of them. Their biogenesis is not well-known, but it is thought that many lincRNAs originate from genomic duplication of coding material, resulting in pseudogenes, gene copies that lose their original function and can accumulate mutations. While most pseudogenes eventually stop producing a transcript and become erased by mutations, many of these pseudogene-based lincRNAs keep similarity to the parental gene from which they originated, possibly for functional reasons. For example, they can act as decoys for miRNAs targeting the parental gene. Enrichment analysis of fun…
Co-regulation of paralog genes in the three-dimensional chromatin architecture.
2016
Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression acco…