Microalgae contribute significantly to carbon fixation on Earth. Global warming influences their physiology and growth rates. To understand algal short-term acclimation and adaptation to changes in ambient temperature, it is essential to identify and characterize the molecular components that sense small temperature changes as well as the downstream signaling networks and physiological responses. Here, we used the green biflagellate alga as a model system in which to study responses to temperature. We report that an RNA recognition motif (RRM)-containing RNA-binding protein, Musashi, occurs in 25 putative splice variants. These variants bear one, two, and three RRM domains or even lack RRM domains. The most abundant Musashi variant, 12, with a molecular mass of 60 kD, interacts with two clock-relevant members of RNA metabolism, the subunit C3 of the RNA-binding protein CHLAMY1 and the 5'-3' exoribonuclease XRN1. These proteins are able to integrate temperature information by up- or down-regulation of their protein levels in cells grown at low (18°C) or high (28°C) temperature. We further show that the 60-kD Musashi variants with three RRM domains can bind to (UG) repeat-containing RNAs and are up-regulated in cells grown at a higher temperature during early night. Intriguingly, the 60-kD Musashi variant 12, as well as C3 and XRN1, confer thermal acclimation to , as shown with mutant lines. Our data suggest that these three proteins of the RNA metabolism machinery are key members of the thermal signaling network in .
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http://dx.doi.org/10.1104/pp.18.00972 | DOI Listing |
PLoS One
December 2024
Neuroscience, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey, United States of America.
Ataxin-2 is a protein containing a polyQ extension and intermediate length of polyQ extensions increases the risk of Amyotrophic Lateral Sclerosis (ALS). Down-regulation of Ataxin-2 has been shown to mitigate TDP-43 proteinopathy in ALS models. To identify alternative therapeutic targets that can mitigate TDP-43 toxicity, we examined the interaction between Ataxin-2 and TDP-43.
View Article and Find Full Text PDFWiley Interdiscip Rev RNA
December 2024
Chemical Genomics Centre of the Max Planck Society, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
The RNA recognition motif (RRM) is the most common RNA binding domain found in the human proteome. RRM domains provide RNA-binding proteins with sequence specific RNA recognition allowing them to participate in RNA-centric processes such as mRNA maturation, translation initiation, splicing, and RNA degradation. They are drivers of various diseases through overexpression or mutation, making them attractive therapeutic targets and addressing these proteins through their RRM domains with chemical compounds is gaining ever more attention.
View Article and Find Full Text PDFRNA
December 2024
Heinrich Heine University Dusseldorf, Institute of Microbiology;
The entire RNA lifecycle, spanning from transcription to decay, is intricately regulated by RNA-binding proteins (RBPs). To understand their precise functions, it is crucial to identify direct targets, pinpoint their exact binding sites, and unravel the underlying specificity in vivo. Individual-nucleotide resolution UV crosslinking and immunoprecipitation 2 (iCLIP2) is a state-of-the-art technique that enables the identification of RBP binding sites at single-nucleotide resolution.
View Article and Find Full Text PDFJ Mol Biol
November 2024
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801, United States; Carl R. Woese Institute for Genomic Biology, 1206 West Gregory Drive, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801, United States. Electronic address:
Proteins with intrinsically disordered regions (IDR) play diverse functions in regulating gene expression in the cell. Many of these proteins interact with cytoplasmic ribosomes. However, the molecular functions related to the interactions are largely unclear.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
Deposits of aggregated TAR DNA-binding protein 43 (TDP-43) in the brain are associated with several neurodegenerative diseases. It is well established that binding of RNA/DNA to TDP-43 can prevent TDP-43 aggregation, but an understanding of the structure(s) and conformational dynamics of TDP-43, and TDP-43-RNA complexes, is lacking, including knowledge of how the solution environment modulates these properties. Here, we address this challenge using hydrogen-deuterium exchange-mass spectrometry.
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