Glucose-Regulated Phosphorylation of the PUF Protein Puf3 Regulates the Translational Fate of Its Bound mRNAs and Association with RNA Granules

In neurons, mRNAs are transported to distal sites to allow for localized protein synthesis. There are many diverse mechanisms underlying this transport. For example, an individual mRNA can be transported in an RNA transport particle that is tailored to the individual mRNA and its associated binding proteins. In contrast, some mRNAs are transported in liquid-liquid phase separated structures called neuronal RNA granules that are made up of multiple stalled polysomes, allowing for rapid initiation-independent production of proteins required for synaptic plasticity. Moreover, neurons have additional types of liquid-liquid phase–separated structures containing mRNA, such as stress granules and P bodies. This chapter discusses the relationships between all of these structures, what proteins distinguish them, and the possible roles they play in the complex control of mRNA translation at distal sites that allow neurons to use protein synthesis to refine their local proteome in many different ways.

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RNA granules: the clock within

Nature Reviews Molecular Cell Biology ◽

10.1038/nrm3684 ◽

2013 ◽

Vol 14 (11) ◽

pp. 689-689 ◽

Cited By ~ 1

Author(s):

Kim Baumann

Keyword(s):

Rna Granules

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Poly(ADP-ribose): An organizer of cellular architecture

The Journal of Cell Biology ◽

10.1083/jcb.201402114 ◽

2014 ◽

Vol 205 (5) ◽

pp. 613-619 ◽

Cited By ~ 117

Author(s):

Anthony K.L. Leung

Keyword(s):

Dna Repair ◽

Self Assembly ◽

Structural Diversity ◽

Low Complexity ◽

Cellular Organization ◽

Rna Granules ◽

Cellular Architecture ◽

Spindle Poles ◽

Granule Proteins

Distinct properties of poly(ADP-ribose)—including its structural diversity, nucleation potential, and low complexity, polyvalent, highly charged nature—could contribute to organizing cellular architectures. Emergent data indicate that poly(ADP-ribose) aids in the formation of nonmembranous structures, such as DNA repair foci, spindle poles, and RNA granules. Informatics analyses reported here show that RNA granule proteins enriched for low complexity regions, which aid self-assembly, are preferentially modified by poly(ADP-ribose), indicating how poly(ADP-ribose) could direct cellular organization.

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Multi-omics profiling of U2AF1 mutants dissects pathogenic mechanisms affecting RNA granules in myeloid malignancies

10.1101/2021.04.22.441020 ◽

2021 ◽

Author(s):

Giulia Biancon ◽

Poorval Joshi ◽

Joshua T Zimmer ◽

Torben Hunck ◽

Yimeng Gao ◽

...

Keyword(s):

Rna Binding ◽

Specific Binding ◽

Aberrant Splicing ◽

Binding Model ◽

Full Spectrum ◽

Myeloid Malignancies ◽

Rna Granules ◽

Rna Biology ◽

Site Recognition

AbstractSomatic mutations in splicing factors are of significant interest in myeloid malignancies and other cancers. U2AF1, together with U2AF2, is essential for 3’ splice site recognition. U2AF1 mutations result in aberrant splicing, but the molecular mechanism and the full spectrum of consequences on RNA biology have not been fully elucidated to date. We performed multi-omics profiling of in vivo RNA binding, splicing and turnover for U2AF1 S34F and Q157R mutants. We dissected specific binding signals of U2AF1 and U2AF2 and showed that U2AF1 mutations individually alter U2AF1-RNA binding, resulting in defective U2AF2 recruitment. We demonstrated a complex relationship between differential binding and splicing, expanding upon the currently accepted loss-of-binding model. Finally, we observed that U2AF1 mutations increase the formation of stress granules in both cell lines and primary acute myeloid leukemia samples. Our results uncover U2AF1 mutation-dependent pathogenic RNA mechanisms and provide the basis for developing targeted therapeutic strategies.

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