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Related Concept Videos

Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
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After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
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In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
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Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
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The Rab5 effector FERRY links early endosomes with mRNA localization.

Jan S Schuhmacher1, Susanne Tom Dieck2, Savvas Christoforidis3

  • 1Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

Molecular Cell
|June 2, 2023
PubMed
Summary

Researchers discovered the FERRY complex, an endosomal protein that transports mRNAs and ribosomes. This finding is crucial for understanding localized translation and its role in cell function and disease.

Keywords:
RNA binding proteinRab5 effectorendocytosismRNA localizationmitochondrianeuronsprotein complex

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Localized translation is essential for polarized cells, requiring precise mRNA and ribosome distribution.
  • The molecular mechanisms governing mRNA and ribosome transport are not fully understood.

Purpose of the Study:

  • To identify novel molecular players involved in mRNA and ribosome transport and localization.
  • To elucidate the function of the newly discovered FERRY complex in cellular mRNA distribution.

Main Methods:

  • Identification and characterization of the FERRY complex as a Rab5 effector.
  • Investigating FERRY's direct interaction with mRNAs and ribosomes.
  • Analyzing the impact of FERRY subunit deletion on transcript localization and levels.
  • Co-localization studies in neurons to assess FERRY, mRNA, and mitochondrial proximity.

Main Results:

  • The five-subunit FERRY complex directly recruits mRNAs and ribosomes to early endosomes.
  • FERRY exhibits preferential binding to specific transcripts, including those for mitochondrial proteins.
  • FERRY deletion disrupts endosomal transcript localization and affects mRNA levels.
  • Genetic FERRY disruption is linked to severe brain damage in clinical studies.
  • In neurons, FERRY-bound endosomes carrying mRNA are located near mitochondria.

Conclusions:

  • The FERRY complex acts as a crucial intermediary, linking endosomes to mRNA and ribosome transport.
  • FERRY transforms endosomes into dynamic carriers for mRNA distribution, impacting cellular function.
  • Dysregulation of FERRY-mediated mRNA transport is implicated in neurological disorders.