Papers by Xavier Hernandez Alias
Nucleic Acids Research
Transfer RNA (tRNA) utilizes multiple properties of abundance, modification, and aminoacylation i... more Transfer RNA (tRNA) utilizes multiple properties of abundance, modification, and aminoacylation in translational regulation. These properties were typically studied one-by-one; however, recent advance in high throughput tRNA sequencing enables their simultaneous assessment in the same sequencing data. How these properties are coordinated at the transcriptome level is an open question. Here, we develop a single-read tRNA analysis pipeline that takes advantage of the pseudo single-molecule nature of tRNA sequencing in NGS libraries. tRNAs are short enough that a single NGS read can represent one tRNA molecule, and can simultaneously report on the status of multiple modifications, aminoacylation, and fragmentation of each molecule. We find correlations among modification-modification, modification-aminoacylation and modification-fragmentation. We identify interdependencies among one of the most common tRNA modifications, m1A58, as coordinators of tissue-specific gene expression. Our me...
Genes enriched in A/T-ending codons are co-regulated and conserved across mammals
Cell Systems
Background: In a wide variety of organisms, synonymous codons are used with different frequencies... more Background: In a wide variety of organisms, synonymous codons are used with different frequencies, a phenomenon known as codon bias that plays an important role in determining expression levels. However, the importance of codon bias to facilitate the simultaneous turnover of thousands of protein-coding transcripts to bring about phenotypic changes in cellular programs such as development, has not yet been investigated in detail. Results: Here, we discover that genes with A/T-ending codon preferences are expressed coordinately and display a high codon conservation in mammals. This feature is not observed in genes enriched in G/C-ending codons. A paradigmatic case of this phenomenon is KRAS, from the RAS family, an A/T-rich gene with a high codon conservation (95%) in comparison to HRAS (76%). Also, we find that genes with similar codon composition are more likely to be part of the same protein complex, and that genes with A/T-ending codons are more prone to form protein complexes tha...
Cancers, 2021
With most cancer-related deaths resulting from metastasis, the development of new therapeutic app... more With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identif...
Proceedings of the National Academy of Sciences, 2020
Significance In light of the genetic code, combinations of three nucleotides which are known as s... more Significance In light of the genetic code, combinations of three nucleotides which are known as synonymous codons, can give rise to the same amino acid. Despite the homology at the protein level, these different codons are recognized distinctly by the translational machinery. The unequal use of synonymous codons influences protein expression. Surprisingly, we find that the coding sequences of KRAS and other frequently mutated cancer genes are adapted to be efficiently translated in proliferating cells in comparison to their family counterparts. Our work contributes to the unsolved question of why in tumors some members of cancer gene families show a higher mutation rate than their family counterparts. Thus, our results elucidate the relationship between tRNA expression, codon usage, and oncogenicity.
Cell Reports, 2021
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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Papers by Xavier Hernandez Alias