Dynamic Recruitment of Single RNAs to Processing Bodies Depends on RNA Functionality

Pitchiaya, Sethuamasundaram; Mourao, Marcio Duarte Albasini; Jalihal, Ameya P.; Xiao, Lanbo; Jiang, Xia; Chinnaiyan, Arul M.; Schnell, Santiago; Walter, Nils G.

doi:10.2139/ssrn.3224532

Cited by 18 publications

(30 citation statements)

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“…In a previous study (Pitchiaya et al, 2019), we observed that osmotic stress leads to phase separation of DCP1A, a non-catalytic protein component of the eukaryotic decapping complex and conserved PB marker (Anderson and Kedersha, 2009). To study the intracellular kinetics of de novo PB and SG formation in response to stress more broadly, we subjected U2OS cells to osmotic and oxidative stressors, and performed fixed-cell protein immunofluorescence (IF) or combined IF and RNA fluorescent in situ hybridization (RNA-FISH) before and after the stressors (Figure 1).…”

Section: Changes In Extracellular Tonicity Induce Rapid and Reversible Intracellular Phase Separation Of Dcp1a But Not Sg Markersmentioning

confidence: 88%

Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change

et al. 2020

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Lead contact *equal contribution, listed by alphabetical order . CC-BY-NC-ND 4.0 International license a certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under GRAPHICAL ABSTRACT IN BRIEF Cells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.

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Section: Changes In Extracellular Tonicity Induce Rapid and Reversible Intracellular Phase Separation Of Dcp1a But Not Sg Markersmentioning

confidence: 88%

Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change

et al. 2020

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“…Supporting different outcomes upon miRISC binding to coding and noncoding transcripts is recent evidence that these two classes of transcripts have distinct interaction dynamics with processing bodies (PB; Pitchiaya et al , 2019), the subcellular compartment where miRNA‐dependent destabilization is thought to occur (Eulalio et al , 2007). Specifically, and in contrast to miRNA‐bound mRNAs, which localize to the core of PB, miRNA‐bound lncRNAs interact transiently and tend to locate to the PB periphery, a pattern that might reflect missing interactions with other molecular factors involved in miRNA‐dependent regulation (Pitchiaya et al , 2019). One such factor could be DDX6, a PB‐localized dead box helicase that links miRNA‐dependent translation inhibition and decay (Chu & Rana, 2006; Chen et al , 2014; Rouya et al , 2014).…”

Section: Discussionmentioning

confidence: 99%

Translation is required for miRNA‐dependent decay of endogenous transcripts

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Post-transcriptional repression of gene expression by miRNAs occurs through transcript destabilization or translation inhibition. mRNA decay is known to account for most miRNA-dependent repression. However, because transcript decay occurs co-translationally, whether target translation is a requirement for miRNA-dependent transcript destabilization remains unknown. To decouple these two molecular processes, we used cytosolic long noncoding RNAs (lncRNAs) as models for endogenous transcripts that are not translated. We show that, despite interacting with the miRNA-loaded RNA-induced silencing complex, the steady-state abundance and decay rates of these transcripts are minimally affected by miRNA loss. To further validate the apparent requirement of translation for miRNA-dependent decay, we fused two lncRNA candidates to the 3'-end of a proteincoding gene reporter and found this results in their miRNA-dependent destabilization. Further analysis revealed that the few natural lncRNAs whose levels are regulated by miRNAs in mESCs tend to associate with translating ribosomes, and possibly represent misannotated micropeptides, further substantiating the necessity of target translation for miRNA-dependent transcript decay. In summary, our analyses suggest that translation is required for miRNA-dependent transcript destabilization, and demonstrate that the levels of coding and noncoding transcripts are differently affected by miRNAs.

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“…Early work in P‐bodies provided evidence that these structures could act as sites of mRNA decay (Parker & Sheth, 2007; Sheth & Parker, 2003), and smaller P‐bodies appear to be suited to stimulating mRNA decay whereas larger P‐bodies may be better for storage (Pitchiaya et al, 2019). More recent work in P‐bodies and stress granules suggests that these structures can also act as storage sites for mRNAs upon cellular stress (Hubstenberger et al, 2017; Ivanov, Kedersha, & Anderson, 2019; Padron, Iwasaki, & Ingolia, 2019; Protter & Parker, 2016).…”

Section: Introductionmentioning

confidence: 99%

Phase‐separated bacterial ribonucleoprotein bodies organize mRNA decay

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In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated proteins. Recent advances in bacterial cell biology have shown that RNA degradosomes can assemble into phase-separated structures, termed bacterial ribonucleoprotein bodies (BR-bodies), with many analogous properties to eukaryotic processing bodies and stress granules. This review will highlight the functional role that BR-bodies play in the mRNA decay process through its organization into a membraneless organelle in the bacterial cytoplasm. This review will also highlight the phylogenetic distribution of BRbodies across bacterial species, which suggests that these phase-separated structures are broadly distributed across bacteria, and in evolutionarily related mitochondria and chloroplasts.

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Dynamic Recruitment of Single RNAs to Processing Bodies Depends on RNA Functionality

Cited by 18 publications

References 0 publications

Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change

Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change

Translation is required for miRNA‐dependent decay of endogenous transcripts

Phase‐separated bacterial ribonucleoprotein bodies organize mRNA decay

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