Biology subjects

Harvey, S. E.

Publications and source records attributed to Harvey, S. E..

3 recordsLinked to original sources

bioRxiv2025

Quantifying Differences in Neural Population Activity With Shape Metrics

Quantifying differences across species and individuals is fundamental to many fields of biology. However, it remains challenging to draw detailed functional comparisons between large populations of interacting neurons. Here, we introduce a general framework for comparing neural population activity in terms of shape distances. This approach defines similarity in terms of explicit geometric transformations, which can be flexibly specified to obtain different measures of population-level neural similarity. Moreover, differences between systems are defined by a distance that is symmetric and satisfies the triangle inequality, enabling downstream analyses such as clustering and nearest-neighbor regression. We demonstrate this approach on datasets spanning multiple behavioral tasks (navigation, passive viewing of images, and decision making) and species (mice and non-human primates), highlighting its potential to measure functional variability across subjects and brain regions, as well as its ability to relate neural geometry to animal behavior.

neuroscience↗

bioRxiv2023

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity

RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing. In this study, we identify hnRNPM as an essential RNA binding protein that suppresses cryptic splicing through binding to deep introns, preserving transcriptome integrity. Long interspersed nuclear elements (LINEs) harbor large amounts of pseudo splice sites in introns. hnRNPM preferentially binds at intronic LINEs and represses LINE-containing pseudo splice site usage for cryptic splicing. Remarkably, a subgroup of the cryptic exons can form long dsRNAs through base-pairing of inverted Alu transposable elements scattered in between LINEs and trigger interferon immune response, a well-known antiviral defense mechanism. Notably, these interferon-associated pathways are found to be upregulated in hnRNPM-deficient tumors, which also exhibit elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity. Targeting hnRNPM in tumors may be used to trigger an inflammatory immune response thereby boosting cancer surveillance.

genomics↗

bioRxiv2018

A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes

RNA secondary structures have been increasingly recognized to play an important regulatory role in post-transcriptional gene regulation. We recently showed that RNA G-quadruplexes, which serve as cis-elements to recruit splicing factors, play a critical role in regulating alternative splicing during the epithelial-mesenchymal transition. In this study, we performed a high-throughput screen using a dual-color splicing reporter to identify chemical compounds capable of regulating G-quadruplex-dependent alternative splicing. We identify emetine and its analog cephaeline as small molecules that disrupt RNA G-quadruplexes, resulting in inhibition of G-quadruplex-dependent alternative splicing. Transcriptome analysis reveals that emetine globally regulates alternative splicing, including splicing of variable exons that contain splice site-proximal G-quadruplexes. These data suggest the use of emetine and cephaeline for investigating mechanisms of G-quadruplex-associated alternative splicing.

cell biology↗