Biology subjects

Olguin, P.

Publications and source records attributed to Olguin, P..

3 recordsLinked to original sources

bioRxiv2022

Developmentally regulated alternate 3' end cleavage of nascent transcripts controls dynamic changes in protein expression in an adult stem cell lineage

Alternative polyadenylation (APA) generates transcript isoforms that differ in the position of the 3 cleavage site, resulting in the production of mRNA isoforms with different length 3UTRs. Although widespread, the role of APA in the biology of cells, tissues and organisms has been controversial. We identified over 500 Drosophila genes that express mRNA isoforms with a long 3UTR in proliferating spermatogonia but a short 3UTR in differentiating spermatocytes due to APA. We show that the stage-specific choice of the 3 end cleavage site can be regulated by the arrangement of a canonical polyadenylation signal (PAS) near the distal cleavage site but a variant or no recognizable PAS near the proximal cleavage site. The emergence of transcripts with shorter 3UTRs in differentiating cells correlated with changes in expression of the encoded proteins, either from off in spermatogonia to on in spermatocytes or vice versa. Polysome gradient fractionation revealed over 250 genes where the long 3UTR versus short 3UTR mRNA isoforms migrated differently, consistent with dramatic stage-specific changes in translation state. Thus, the developmentally regulated choice of an alternative site at which to make the 3end cut that terminates nascent transcripts can profoundly affect the suite of proteins expressed as cells advance through sequential steps in a differentiation lineage.

developmental biology↗

bioRxiv2022

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

Actin filament polymerization can be branched or linear, which depends on the associated regulatory proteins. Competition for Actin monomers occurs between proteins that induce branched or linear actin polymerization. Cell specialization requires the regulation of actin filaments to allow the formation of cell-type specific structures, like cuticular hairs in Drosophila, formed by linear actin filaments. Here, we report the functional analysis of CG34401/pelado, a gene encoding a SWIM domain containing protein, conserved throughout the animal kingdom. Mutant pelado epithelial cells display actin hair elongation defects. This phenotype is reversed by increasing Actin monomer levels or by either pushing linear actin polymerization or reducing branched actin polymerization. The same behavior occurs in hemocytes, where Pelado is essential to induce filopodia, a linear actin-based structure. We further show that this function of Pelado, ZSWIM8 in mammals, is conserved in human cells, where Pelado inhibits branched actin polymerization in a cell migration context. In summary, our data indicate that the function of Pelado/ZSWIM8 in regulating actin cytoskeletal dynamics is conserved, favoring linear actin polymerization at the expense of branched filaments.

cell biology↗

bioRxiv2020

Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster

The mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction has genotype-specific effects on variation in sleep behavior and brain morphology. We mapped genes associated with sleep sensitivity to early-life nutrition, which were enriched for protein-protein interactions responsible for translation, endocytosis regulation, ubiquitination, lipid metabolism, and neural development. By manipulating the expression of candidate genes in the mushroom bodies and all neurons, we confirm that genes regulating neural development, translation and insulin signaling contribute to the variable response of sleep and brain morphology to early-life nutrition. We show that the interaction between differential expression of candidate genes with nutritional restriction in early life resides in the mushroom bodies or other neurons, and that these effects are sex specific. Natural variation in genes that control the systemic response to nutrition and brain development and function interact with early-life nutrition in different types of neurons to contribute to the variation of brain morphology and adult sleep behavior.

genetics↗