Biology subjects

Tallo-Parra, M.

Publications and source records attributed to Tallo-Parra, M..

4 recordsLinked to original sources

bioRxiv2026

Evolutionary emergence and preservation of microproteins encoded by upstream ORFs

The analysis of ribosome profiling (Ribo-Seq) data has provided evidence that many eukaryotic mRNAs contain translated upstream or downstream ORFs (uORFs/dORFs), but the biological significance of this translation activity remains, for the most part, unknown. One of the principal limitations has been the lack of Ribo-Seq data from several closely related species, precluding the identification of cases in which translation is phylogenetically conserved. Here, by combining Ribo-Seq data from 100 different experiments, we identify 2,332 translated uORFs and 1,008 translated dORFs in S. cerevisiae, which result in microproteins that tend to be highly hydrophobic or positively charged. To study their phylogenetic conservation, we have generated Nanopore direct RNA sequencing data, together with Ribo-Seq data, from six additional Saccharomyces species, spanning an evolutionary period of around 16 million years. We have identified 195 translated S. cerevisiae uORFs that are also translated in other Saccharomyces species; these uORFs are translated at levels comparable to the main coding sequence and display signatures of purifying selection at the level of the encoded microproteins. In contrast, dORFs are translated at very low levels and they are rarely conserved, suggesting much more limited microprotein functionalization. We have also discovered that uORF translation is associated with the formation of alternative transcript isoforms encompassing the region containing the uORFs but not the main protein coding sequence, implying that some microproteins can be produced independently of the main protein product. This work significantly advances our understanding of how initially pervasive uORF translation can result in new microproteins, providing many new candidates for further functional studies.

genomics↗

bioRxiv2026

Arbovirus persistence in mosquitoes is characterized by translation repression of viral RNAs

Arboviruses induce acute lytic infection in human cells but establish persistent infection in their mosquito vectors, a viral strategy that is essential for sustained viral transmission. How mosquito cells maintain continuous production of viral progeny without compromising host cell viability remains a fundamental unresolved question. Because arbovirus replication in human cells relies on viral takeover of the host translational machinery, we investigated how translation is regulated during persistent infection in mosquito cells using chikungunya virus (CHIKV) as a model. A temporal analysis of viral RNA translation in RNAi-competent and RNAi-deficient Aedes albopictus cells revealed that persistence was associated with reduced viral protein production resulting from translation repression of viral RNAs. Subcellular localization analyses of the viral protein nsP2 and LC-MS/MS analyses of host tRNAs showed that, in contrast to human cells, CHIKV infection in mosquito cells neither induced nuclear relocalization of viral nsP2 to induce global host mRNA depletion, nor reshaped the tRNA modification landscape to compensate for the suboptimal codon usage of viral RNAs. Together, our results indicate that persistent infection in mosquito cells is characterized by a balanced host-virus translational state, in which limited viral translation is maintained while viral takeover of the host translational machinery is avoided. Notably, translation repression of viral RNAs was also observed during Zika virus (ZIKV) infection, suggesting that this mechanism may represent a general RNAi-independent feature of arbovirus persistence in mosquito cells.

microbiology↗

bioRxiv2025

Translational repression of viral RNA mediates arbovirus persistence in mosquitoes

Persistent infection of mosquito cells is essential for the transmission of arboviruses, yet how these viruses produce sufficient progeny without compromising host cell fitness remains unclear. Arbovirus genomes exhibit suboptimal codon usage for both human and mosquito hosts, raising questions about how they achieve efficient translation in such distinct cellular environments. Using chikungunya virus (CHIKV) as a model, we conducted a temporal, genome-wide analysis of transcription, translation, and tRNA modifications in Aedes albopictus C6/36 cells. Unlike in human cells, CHIKV infection does not alter the tRNA modification landscape in mosquitoes to overcome codon bias, nor does it induce widespread degradation of host transcripts. Instead, viral persistence is marked by a progressive, virus-specific repression of CHIKV RNA translation, occurring alongside a recovery of host mRNA translation. This translational balance, maintained independently of the RNAi system, enables sustained viral production without major disruption to host gene expression. Our findings identify translational control as a central mechanism underlying persistent arbovirus infection in mosquito cells.

microbiology↗

bioRxiv2020

Host-derived Circular RNAs Display Proviral Activities in Hepatitis C Virus - Infected Cells

Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Surprisingly, circPSD3 also inhibited the cellular nonsense-mediated decay (NMD) pathway in liver cells. Thus, enhanced abundance of circPSD3 in virus-infected cells aids in viral replication and likely contributes to the known inhibition of NMD in HCV-infected cells. Findings from the global analyses of the circular RNA landscape argue pro-, and likely, anti-viral functions are executed by circRNAs that modulate both viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis. Author SummaryUsually, cells are infected by one or a few virus particles that carry genomes with limited expression capacity. Thus, the expression of viral genomes has to compete with a sea of cellular components that aid in viral translation, replication and virion production. Depending on their lifestyle, viruses have evolved to avoid or to subvert cellular pathways, especially those that display anti-viral functions. Host-derived circular RNA molecules have recently been discovered in the cytoplasm of cells, although, as-of yet, few functions have been assigned to them. Here, we describe alterations in the circular RNA landscape in hepatitis C virus-infected liver cells. Up-regulated and down-regulated circular RNAs were identified, and three of the upregulated RNAs were shown to promote HCV infection. One of them, circPSD3, inhibited the cellular nonsense-mediated RNA decay that is a powerful antiviral response in infected cells. Because circular RNAs are more stable than linear RNAs, they may have important functions during viral infection, dictating the outcomes of innate immune responses and viral pathogenesis.

microbiology↗