mRNA Localization: Gene Expression in the Spatial Dimension

Martin, Kelsey C.; Ephrussi, Anne

doi:10.1016/j.cell.2009.01.044

Cited by 969 publications

(908 citation statements)

References 100 publications

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“…18 A signaling event often precedes the switch of localized mRNAs from repression to translation, followed by granule disassembly. 9,15,91 This topic has been well covered elsewhere, 92 thus the focus here will be on how granule formation may contribute to localization.…”

Section: Role Of Mrnp Granules In Mrna Localizationmentioning

confidence: 99%

“…Some of the earliest attempts at purifying nuclear transport granules identified large complexes (>1000S), with presumably multiple mRNAs. 23 Staining with in situ probes against common leader sequence or poly-adenylated mRNAs also suggest a large population of mRNAs reside in germ granules, 92,93 as well as Pbodies and stress granules. 24,25 Approaches using specific mRNA labeling also shows co-migration of several mRNA species in neuronal granule subtypes, 95 and the Ash1 locasome in yeast, 96,97 and many mRNA species individually localize in stress granules or Pbodies under identical conditions.…”

Section: Role Of Mrnp Granules In Mrna Localizationmentioning

confidence: 99%

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mRNP granules

2014

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Section: Role Of Mrnp Granules In Mrna Localizationmentioning

confidence: 99%

Section: Role Of Mrnp Granules In Mrna Localizationmentioning

confidence: 99%

mRNP granules

2014

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“…Once localized, they may be activated by one of several alternative mechanisms. [69][70][71][72] Translation of mRNAs that are packaged into RNPs are regulated at multiple stages of their translation. However the most common mechanism involve regulation of initiation step of mRNA translation.…”

Section: Rna Regulation Is Central To Long-term Memory Formationmentioning

confidence: 99%

“…RNA granules therefore function both in RNA localization as well as in local translation, enabling spatiotemporal regulation of protein synthesis. 71,169,170 Much of what is known about RNA granule functions comes from studies of P-bodies (PBs) and stress granules (SGs) in eukaryotic cells that contain non-translating mRNAs, together with various translational regulators. PBs contain RNAdegradative enzymes and translational repressors whereas SGs contain translational initiation factors stalled at specific stage of translational initiation.…”

Section: Prion Like Domains In Neuronal Rnp Mediated Translationmentioning

confidence: 99%

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Sudhakaran

Ramaswami

2016

RNA Biology

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Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

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“…Collectively, these mechanisms regulate diverse aspects of mRNA fate within the cell, including its translation, degradation and subcellular localization (3)(4)(5). Modulating RNA translation and degradation via small molecule-RNA interactions has been recently emphasized (6).…”

Section: Introductionmentioning

confidence: 99%

Engineering a Direct and Inducible Protein−RNA Interaction To Regulate RNA Biology

Belmont

Niles

2010

ACS Chem. Biol.

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The importance and pervasiveness of naturally occurring regulation of RNA function in biology is increasingly being recognized. A common mechanism uses inducible protein-RNA interactions to shape diverse aspects of cellular RNA fate. Recapitulating this regulatory mode in cells using a novel set of protein-RNA interactions is appealing given the potential to subsequently modulate RNA biology in a manner decoupled from endogenous cellular physiology. Achieving this outcome, however, has previously proven challenging. Here, we describe a ligand-responsive protein-RNA interaction module, which can be used to target a specific RNA for subsequent regulation. Using the Systematic Evolution of Ligands by Exponential Enrichment method, RNA aptamers binding to the bacterial Tet Repressor protein (TetR) with low-to sub-nanomolar affinities were obtained. This interaction is reversibly controlled by tetracycline in a manner analogous to the interaction of TetR with its cognate DNA operator. Aptamer minimization and mutational analyses support a functional role for two conserved sequence motifs in TetR binding. As an initial illustration of using this system to achieve protein-based regulation of RNA function in living cells, insertion of a TetR aptamer into the 5'-UTR of a reporter mRNA confers post-transcriptionally regulated, ligandinducible protein synthesis in E. coli. Altogether, these results define and validate an inducible protein-RNA interaction module that incorporates desirable aspects of a ubiquitous mechanism for regulating RNA function in Nature, and which can be used as a foundational interaction for functionally and reversibly controlling the multiple fates of RNA in cells.3

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mRNA Localization: Gene Expression in the Spatial Dimension

Cited by 969 publications

References 100 publications

mRNP granules

mRNP granules

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Engineering a Direct and Inducible Protein−RNA Interaction To Regulate RNA Biology

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