Biology subjects

Coyne, S.

Publications and source records attributed to Coyne, S..

3 recordsLinked to original sources

bioRxiv2025

Direct and indirect regulation of fetal globin transcript by RNA-binding protein IGF2BP1

Despite extensive investigation, the molecular control of developmental hemoglobin expression remains incompletely elucidated. Hemoglobin switching is controlled by transcription factors, miRNAs, and RNA-binding proteins (RBPs) that enforce gene regulatory changes through development. Here we examine the role of the heterochronically silenced N-6 methyladenosine (m6A) RNA-binding protein IGF2BP1 that was previously described to regulate HBG1/2 indirectly by suppressing BCL11A expression through an unknown mechanism. We find that IGF2BP1 binds and activates HIC2, itself a BCL11A repressor. Furthermore, we identify that IGF2BP1 plays a BCL11A-independent role by direct binding to HBG1/2 to promote its translation. Stop codon-proximal m6A-modified coding sequences within HBG2 transcripts are necessary and sufficient for direct positive regulation mediated by IGF2BP1. This work deepens the mechanistic understanding of hemoglobin switching and suggests a physical relationship between heterochronic RBPs and globin transcripts.

genetics↗

bioRxiv2025

Bird occurrence and trophic interactions vary across gradients of tree diversity and microclimate in a planted forest

Deforestation reshuffles communities across landscapes with myriad consequences for ecosystem function. Following deforestation, rapid exposure to novel microclimates can act as a strong environmental filter, favoring warm-adapted species and decoupling trophic interactions. Forest restoration may partly reverse this process through increased habitat structure, food resources, and buffering of microclimates - each potentially modified by tree diversity. Despite growing evidence that tree diversity and cool microclimates help maintain animal diversity in natural forests, less is known about how these factors shape species assemblages or multitrophic dynamics in restoration areas. Here, using surveys and two field experiments within a long-term tree planting experiment, we assessed the relative effects of tree diversity, forest structure, and associated microclimate on fine-scale space use by birds and their top-down impacts on insects. Surveys showed that fine-scale occurrences of birds increased in cooler plots, which were associated with higher tree diversity and structural complexity. The strength of microclimate effects on bird occurrences was strongest for species that are forest specialists. To assess risk to insect herbivores from avian predation, we used a sentinel prey experiment and found that predation risk increased in warmer plots, counter to our expectations based on bird surveys. Last, we examined top-town effects of bird exclusion on leaf herbivory, finding that skeletonizing patterns of herbivory increased in exclosures and in cooler plots. Taken together, these results suggest that microclimate resulting from variation in forest structure shapes space use of birds at fine scales with complex outcomes for bird-herbivore-tree interactions in planted forests. Active restoration methods that enhance below-canopy cooling may improve biodiversity outcomes and help maintain species interactions that underlie many ecosystem functions.

ecology↗

bioRxiv2024

RNA methylation controls stress granule formation and function during erythropoiesis

Stress granules (SGs) are crucial in RNA regulation, affecting cell fate and function. SGs contain RNAs, some of which can be methylated. We studied m6A RNA modifications during the human CD34+ HSPCs (hCD34+) differentiating into erythroid cells and found that mRNAs encoding many erythroid-specific proteins had decreased methylation during differentiation. Increased levels ALKBH5 demethylase during erythropoiesis controls the levels of the 3UTR methylation of these mRNAs. hCD34+ carrying ALKBH5 mutations demonstrated a block in erythropoiesis, and mass-spectrometry studies of the mutant cells showed decreased levels of SG proteins, including the core granule protein ATXN2. ALKBH5 directly regulates the methylation of the mRNA of ATXN2. ATXN2 overexpression accelerated the erythroid differentiation of HSPCs and rescued the erythroid differentiation of ALKBH5 mutant cells. Very few SGs are found in normal human erythroid progenitors. SGs accumulated substantially in ALKBH5 mutant cells, and surprisingly overexpression of ATNX2 reduced SG numbers to normal. Polysome analysis demonstrated m6A-modified RNAs to be enriched in the pre-polysome fractions that were less translated. This work establishes a mechanism by which during stress, ATXN2 facilitates the release of SG-stored m6A-modified RNAs including erythroid-specific and SG-enriched RNAs that are loaded onto functional ribosomes, allowing better translation and accelerated erythroid differentiation during stress.

cell biology↗