Biology subjects

Marques, A.

Publications and source records attributed to Marques, A..

3 recordsLinked to original sources

bioRxiv2018

Taste Receptor Cells in Mice Express Receptors for the Hormone Adiponectin

The metabolic hormone adiponectin is secreted into the circulation by adipocytes, and mediates key biological functions including insulin sensitivity, adipocyte development, and fatty acid oxidation. Adiponectin is also abundant in saliva, where its functions are poorly understood. Here we report that murine taste receptor cells express adiponectin receptors, and may be a target for salivary adiponectin. Analysis of a transcriptome dataset obtained by RNA-seq analysis of purified circumvallate taste buds, revealed high expression levels for three adiponectin receptor types. Immunohistochemical studies showed that two of these receptors, AdipoR1 and T-cadherin, are localized to subsets of taste receptor cells. Immunofluorescence for T-cadherin was primarily co-localized with the Type 2 taste receptor cell marker phospholipase {beta}2, suggesting that adiponectin signaling could impact sweet, bitter, or umami taste signaling. However, adiponectin null mice showed no differences in taste responsiveness compared to wildtype controls in brief-access taste testing. AAV-mediated overexpression of adiponectin in the salivary glands of adiponectin null mice did result in a small but significant increase in behavioral taste responsiveness to the fat emulsion Intralipid. Together, these results suggest that salivary adiponectin can effect taste receptor cell function, though its impact on taste responsiveness and peripheral taste coding remains unclear.

animal behavior and cognition↗

bioRxiv2018

Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation (OXPHOS) and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

biochemistry↗

bioRxiv2018

An unexpected contribution of lincRNA splicing to enhancer function.

Transcription is common at active mammalian enhancers sometimes giving rise to stable and unidirectionally transcribed enhancer-associated long intergenic noncoding RNAs (elincRNAs). ElincRNA expression is associated with changes in neighboring gene product abundance and local chromosomal topology, suggesting that transcription at these loci contributes to gene expression regulation in cis. Despite the lack of evidence supporting sequence-dependent functions for most elincRNAs, splicing of these transcripts is unexpectedly common. Whether elincRNA splicing is a mere consequence of their cognate enhancer activity or if it directly impacts enhancer-associated cis-regulation remains unanswered.\n\nHere we show that elincRNAs are efficiently and rapidly spliced and that their processing rate is strongly associated with their cognate enhancer activity. This association is supported by: their enrichment in enhancer-specific chromatin signatures; elevated binding of co-transcriptional regulators, including CBP and p300; increased local intra-chromosomal DNA contacts; and strengthened cis-regulation on target gene expression. Using nucleotide polymorphisms at elincRNA splice sites, we found that elincRNA splicing enhances their transcription and directly impacts cis-regulatory function of their cognate enhancers. Importantly, up to 90% of human elincRNAs have nucleotide variants that are associated with both their splicing and the expression levels of their proximal genes.\n\nOur results highlight an unexpected contribution of elincRNA splicing to enhancer function.

genomics↗