Biology subjects

Ooi, F. K.

Publications and source records attributed to Ooi, F. K..

3 recordsLinked to original sources

bioRxiv2021

Tau aggregates are RNA-protein assemblies that mis-localize multiple nuclear speckle components

Tau aggregates contribute to neurodegenerative diseases including frontotemporal dementia and Alzheimers disease (AD). Although RNA promotes tau aggregation in vitro, whether tau aggregates in cells contain RNA is unknown. We demonstrate in cell culture and mouse brains that both cytosolic and nuclear tau aggregates contain RNA, with enrichment for snRNAs and snoRNAs. Nuclear tau aggregates colocalize with and alter the composition, dynamics, and organization of nuclear speckles, which are membraneless organelles involved in pre-mRNA splicing. Moreover, several nuclear speckle components, including SRRM2, mislocalize to cytosolic tau aggregates in cells, mouse brains, and patient brains with AD, frontotemporal dementia (FTD), and corticobasal degeneration (CBD). Consistent with these alterations we observe the presence of tau aggregates is sufficient to alter pre-mRNA splicing. This work identifies tau alteration of nuclear speckles as a feature of tau aggregation that may contribute to the pathology of tau aggregates.

molecular biology↗

bioRxiv2020

Serotonin signaling by maternal neurons upon stress ensures progeny survival

Germ cells are vulnerable to stress. Therefore, how organisms protect their future progeny from damage in a fluctuating environment is a fundamental question in biology. We show that in Caenorhabditis elegans, serotonin released by maternal neurons during stress ensures the viability and stress tolerance of future offspring by enabling the transcription factor HSF1 to alter chromatin in soon-to-be fertilized germ cells by recruiting the histone chaperone FACT, displacing histones, and initiating protective gene expression. Without maternal serotonin signaling by neurons, FACT is not recruited by HSF1 in germ cells, transcription occurs but is delayed, and progeny of stressed C. elegans mothers fail to complete development. Serotonin acts through a signal transduction pathway conserved between C. elegans and mammalian cells to facilitate HSF1 to recruit FACT. These studies uncover a novel mechanism by which stress sensing by neurons is coupled to transcription response times of germ cells to protect future offspring.

cell biology↗

bioRxiv2017

Olfactory learning modulates the expression of molecular chaperones in C. elegans

Learning, a process by which animals modify their behavior as a result of experience, allows organisms to synthesize information from their surroundings to acquire resources and predict danger. Here we show that prior encounter with the odor of pathogenic bacteria prepares Caenorhabditis elegans to survive actual exposure to the pathogen by increasing HSF-1-dependent expression of genes encoding molecular chaperones. Learning-mediated enhancement of chaperone gene expression requires serotonin. Serotonin primes HSF-1 to enhance the expression of molecular chaperone genes by promoting its localization to RNA polymerase II-enriched nuclear loci, even prior to transcription. HSF-1-dependent chaperone gene expression ensues, however, only if and when animals encounter the pathogen. Thus, learning equips C. elegans to better survive environmental dangers by pre-emptively and specifically initiating transcriptional mechanisms throughout the whole organism. These studies provide one plausible basis for the protective role of environmental enrichment in disease.

cell biology↗