Biology subjects

Mata, M.

Publications and source records attributed to Mata, M..

3 recordsLinked to original sources

bioRxiv2024

Invariant crossmodal equivalence between objects in rhesus monkeys

After hearing the words Little Red Riding Hood, many humans instantly visualize a girl wearing a red hood in the woods. However, whether nonhuman primates also evoke such visual imagery from sounds remains an open question. We explored this from direct behavioral measurements from two rhesus macaques trained in a delayed crossmodal equivalence task. In each trial, they listened to a sound, such as a monkey vocalization or a word, and three seconds later, selected a visual equivalent out of a pool of 2 to 4 pictures appearing on a touchscreen. We show that monkeys can be trained to discriminate perceptual objects of numerous properties and furthermore that they perceive as invariant different versions of the learned sounds. We propose two potential mechanisms for the brain to solve this task: acoustic memory or visual imagery. After analyzing the monkeys choice accuracies and reaction times in the task, we find that they experience visual imagery when listening to sounds. Therefore, the ability of rhesus monkeys to perceive crossmodal equivalences between learned categories poses rhesus monkeys as an ideal model organism for studying high-order cognitive processes like semantics and conceptual thinking at the single-neuron level.

animal behavior and cognition↗

bioRxiv2018

Impact of a Patient-Derived Hepatitis C Viral RNA Genome with a Mutated MicroRNA Binding Site

Hepatitis C virus (HCV) depends on liver-specific microRNA miR-122 for efficient viral RNA amplification in liver cells. This microRNA interacts with two different conserved sites at the very 5 end of the viral RNA, enhancing miR-122 stability and promoting replication of the viral RNA. Treatment of HCV patients with oligonucleotides that sequester mir-122 resulted in profound loss of viral RNA in phase II clinical trials. However, some patients accumulated in their sera a viral RNA genome that contained a single cytidine to uridine mutation at the third nucleotide from the 5 genomic end. It is shown here that this C3U variant indeed displayed higher rates of replication than that of wild-type HCV when miR-122 abundance is low in liver cells. However, when miR-122 abundance is high, binding of miR-122 to site 1, most proximal to the 5 end in the C3U variant RNA, is impaired without disrupting the binding of miR-122 to site 2. As a result, C3U RNA displays a much lower rate of replication than wild-type mRNA when miR-122 abundance is high in the liver. These findings suggest that sequestration of miR-122 leads to a resistance-associated mutation that has only been observed in treated patients so far, and raises the question about the function of the C3U variant in the peripheral blood.\n\nAuthor SummaryWith the advent of potent direct-acting antivirals (DAA), hepatitis C virus (HCV) can now be eliminated from the majority of patients, using multidrug therapy with DAAs. However, such DAAs are not available for the treatment of most RNA virus infections. The main problem is the high error rate by which RNA-dependent RNA polymerases copy viral RNA genomes, allowing the selection of mutations that are resistant to DAAs. Thus, targeting host-encoded functions that are essential for growth of the virus but not for the host cell offer promising, novel approaches. HCV needs host-encoded microRNA miR-122 for its viral RNA replication in the liver, and depletion of miR-122 in HCV patients results in loss of viral RNA. This study shows that a single-nucleotide mutation in HCV allows viral RNA amplification when miR-122 abundances are low, concomitant with changes in its tropism.

microbiology↗

bioRxiv2017

ciRS-7 exonic sequence is embedded in a long-noncoding RNA locus

ciRS-7 is an intensely studied, highly expressed and conserved circRNA. Essentially nothing is known about its biogenesis, including the location of its promoter. A prevailing assumption has been that ciRS-7 is an exceptional circRNA because it is transcribed from a locus lacking any mature linear RNA transcripts of the same sense. Our interest in the biogenesis of ciRS-7 led us to develop an algorithm to define its promoter. This approach predicted that the human ciRS-7 promoter coincides with that of the long non-coding RNA, LINC00632. We validated this prediction using multiple orthogonal experimental assays. We also used computational approaches and experimental validation to establish that ciRS-7 exonic sequence is embedded in linear transcripts that are flanked by cryptic exons in both human and mouse. Together, this experimental and computational evidence generate a new view of regulation in this locus: (a) ciRS-7 is like other circRNAs, as it is spliced into linear transcripts; (b) expression of ciRS-7 is primarily determined by the chromatin state of LINC00632 promoters; (c) transcription and splicing factors sufficient for ciRS-7 biogenesis are expressed in cells that lack detectable ciRS-7 expression. These findings have significant implications for the study of the regulation and function of ciRS-7, and the analytic framework we developed to jointly analyze RNA-seq and ChlP-seq data reveal the potential for genome-wide discovery of important biological regulation missed in current reference annotations.\n\nAuthor SummarycircRNAs were recently discovered to be a significant product of host gene expression programs but little is known about their transcriptional regulation. Here, we have studied the expression of a well-known circRNA named ciRS-7. ciRS-7 has an unusual function for a circRNA; it is believed to be a miRNA sponge. Previously, ciRS-7 was thought to be transcribed from a locus lacking any mature linear isoforms, unlike all other circular RNAs known to be expressed in human cells. However, we have found this to be false; using a combination of bioinformatic and experimental genetic approaches, in both human and mouse, we discovered that linear transcripts containing the ciRS-7 exonic sequence, linking it to upstream genes. This suggests the potential for additional functional roles of this important locus and provides critical information to begin study on the biogenesis of ciRS-7.

genetics↗