Biology subjects

Curtiss, J.

Publications and source records attributed to Curtiss, J..

3 recordsLinked to original sources

bioRxiv2026

In Step, the sole Drosophila TENT5 poly(A) polymerase, is required for spermatid elongation and individualization

Cytoplasmic poly(A) tail length is a key regulator of mRNA translation and stability, controlled in part by non-canonical poly(A) polymerases of the TENT5 family, which are required for gametogenesis in mice. We characterize the sole Drosophila melanogaster TENT5 ortholog, which we name in step (isep). Although identified as a candidate target of the eye specification factor Eyeless, isep mutants have normal eyes; instead, isep is essential for male fertility. The isep gene and its protein are expressed in spermatocytes and in elongating spermatids and are concentrated at the distal end of spermatid cysts. Mutant spermatids fail to elongate normally and to individualize. Whole-testis poly(A) tail sequencing revealed that, unexpectedly for the loss of a poly(A) polymerase, median tail length increased in mutants, with lengthened transcripts enriched for roles in axoneme assembly. Both wild-type and a predicted catalytically inactive Isep rescued sterility. We propose that Isep controls localized translation of axonemal transcripts at the spermatid tip, largely independently of its poly(A) polymerase activity.

developmental biology↗

bioRxiv2026

The Hidden Landscape of Missed Effects in Human Functional Neuroimaging

Functional neuroimaging aims to uncover brain processes underlying behavior and disease, yet studies are often underpowered to detect these effects. How this literature has shaped our understanding of brain function remains unknown, and little guidance exists for planning better powered studies. An underappreciated barrier is that commonly reported effect sizes across the brain are inflated, biasing study planning. Here, we introduce a correction for this inflation bias and show how more accurate studies can be planned using corrected effect size benchmarks from a mega-analysis of 63 typical studies across seven large datasets (52,979 participants). We find that common methods of planning studies based on uncorrected effects lead to roughly half the expected detections at typical sample sizes, with limited spatial overlap with original findings. These missed effects collectively explain meaningful additional variance in the desired outcome. We show how to recover missed effects by planning not only for power but also for a target number of detections via corrected benchmarks, or by taking a whole-brain approach with multivariate effects that individual research groups can detect (n < 50 compared to n > 1,000 for a typical univariate effect). These findings lay the groundwork for more informed study planning and a richer understanding of the widespread nature of brain effects, with implications for shared challenges (and solutions) across biomedicine.

neuroscience↗

bioRxiv2021

Branched ubiquitin chain binding and deubiquitination by UCH37 facilitate proteasome clearance of stress-induced inclusions

UCH37, also known as UCHL5, is a highly conserved deubiquitinating enzyme (DUB) that associates with the 26S proteasome. Recently it was reported that UCH37 activity is stimulated by branched ubiquitin chain architectures. To understand how UCH37 achieves its unique debranching specificity, we performed biochemical and NMR structural analyses and found that UCH37 is activated by contacts with the hydrophobic patches of both distal ubiquitins that emanate from a branched ubiquitin. In addition, RPN13, which recruits UCH37 to the proteasome, further enhances branched-chain specificity by restricting linear ubiquitin chains from having access to the UCH37 active site. In cultured human cells under conditions of proteolytic stress, we show that substrate clearance by the proteasome is promoted by both binding and deubiquitination of branched polyubiquitin by UCH37. Proteasomes containing UCH37(C88A), which is catalytically inactive, aberrantly retain polyubiquitinated species as well as the RAD23B substrate shuttle factor, suggesting a defect in recycling of the proteasome. These findings provide a foundation to understand how proteasome degradation of substrates modified by a unique ubiquitin chain architecture is aided by a DUB.

biochemistry↗