# Vesicle-coupled mRNA transport and translation govern intracellular organelle networking

**Authors:** Melissa Vázquez-Carrada, Sainath Shanmugasundaram, Sander H J Smits, Lasse van Wijlick, Michael Feldbrügge

PMC · DOI: 10.1038/s44319-025-00666-4 · 2025-12-15

## TL;DR

This review explains how mRNAs are transported and translated on intracellular vesicles, enabling communication and coordination between organelles like mitochondria.

## Contribution

The paper highlights recent discoveries on the mechanisms of mRNA attachment to endosomal and lysosomal membranes for transport and localized translation.

## Key findings

- mRNAs hitchhike on endosomes and lysosomes for transport and localized translation.
- Protein/RNA and protein/protein interactions ensure robust and specific mRNA transport.
- This mechanism supports mitochondrial homeostasis and multi-organelle networking.

## Abstract

Eukaryotic cells are highly compartmentalized, enabling sophisticated division of labour. For example, genetic information is stored in the nucleus while energy is produced in mitochondria. Despite this clear specialisation, compartments depend on intensive communication, including the exchange of metabolites and macromolecules. This is achieved through intracellular trafficking with membranous carriers such as endosomes, which constitute versatile transport vehicles. Key cargos include mRNAs and ribosomes that hitchhike on endosomes, linking RNA and membrane biology. In this review, we summarize recent advances showing how mRNAs are mechanistically attached to membranes of endosomes and lysosomal vesicles and how cargos are identified for transport. The encoded proteins illuminate the biological processes that rely on such spatiotemporal control. This is particularly true for the regulation of subcellular mitochondrial homeostasis, disclosing intensive multi-organelle networking. As a general concept, the underlying protein/protein and protein/RNA interactions exhibit significant redundancy yet are organized in a strict hierarchy with distinct core and accessory functions. This ensures both the robustness and specificity of mRNA hitchhiking.

This review discusses how mRNAs are identified and attached to membranes of endosomes, lysosomes and mitochondria, for their transport and localized translation in organisms ranging from fungi to humans.

## Full-text entities

- **Genes:** tubb3.L (tubulin beta 3 class III L homeolog) [NCBI Gene 495319] {aka tubb3}, PABPC1 (poly(A) binding protein cytoplasmic 1) [NCBI Gene 26986] {aka PAB1, PABP, PABP1, PABPC2, PABPL1}, cd63.S (CD63 molecule S homeolog) [NCBI Gene 380212] {aka cd63}, FHL1 (four and a half LIM domains 1) [NCBI Gene 2273] {aka FCMSU, FHL-1, FHL1A, FHL1B, FLH1A, KYOT}, HNRNPA3 (heterogeneous nuclear ribonucleoprotein A3) [NCBI Gene 220988] {aka 2610510D13Rik, D10S102, FBRNP, HNRPA3}, FUS (FUS RNA binding protein) [NCBI Gene 2521] {aka ALS6, ETM4, FUS1, HNRNPP2, POMP75, TLS}, UBR5 (ubiquitin protein ligase E3 component n-recognin 5) [NCBI Gene 51366] {aka DD5, EDD, EDD1, HYD, NEDSBH}, ARHGEF2 (Rho/Rac guanine nucleotide exchange factor 2) [NCBI Gene 9181] {aka GEF, GEF-H1, GEFH1, LFP40, Lfc, NEDMHM}, RBPJL (recombination signal binding protein for immunoglobulin kappa J region like) [NCBI Gene 11317] {aka RBPL, RBPSUHL, SUHL}, PIKFYVE (phosphoinositide kinase, FYVE-type zinc finger containing) [NCBI Gene 200576] {aka FAB1, HEL37, PIP5K, PIP5K3, ZFYVE29}, RBMS3 (RNA binding motif single stranded interacting protein 3) [NCBI Gene 27303], AKAP1 (A-kinase anchoring protein 1) [NCBI Gene 8165] {aka AKAP, AKAP121, AKAP149, AKAP84, D-AKAP1, PPP1R43}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, KIF1C (kinesin family member 1C) [NCBI Gene 10749] {aka LTXS1, SATX2, SAX2, SPAX2, SPG58}, KIFAP3 (kinesin associated protein 3) [NCBI Gene 22920] {aka FLA3, KAP-1, KAP-3, KAP3, SMAP, Smg-GDS}, TNRC6A (trinucleotide repeat containing adaptor 6A) [NCBI Gene 27327] {aka CAGH26, FAME6, GW1, GW182, TNRC6}, MKRN1 (makorin ring finger protein 1) [NCBI Gene 23608] {aka RNF61}, MICU1 (mitochondrial calcium uptake 1) [NCBI Gene 10367] {aka CALC, CBARA1, EFHA3, MPXPS, ara CALC}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, LARP4 (La ribonucleoprotein 4) [NCBI Gene 113251] {aka PP13296}, TRAK2 (trafficking kinesin protein 2) [NCBI Gene 66008] {aka ALS2CR3, CALS-C, GRIF-1, GRIF1, MILT2, OIP98}, ANXA11 (annexin A11) [NCBI Gene 311] {aka ALS23, ANX11, CAP-50, CAP50, IBMWMA}, VPS8 (VPS8 subunit of CORVET complex) [NCBI Gene 23355] {aka KIAA0804}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALG2 (ALG2 alpha-1,3/1,6-mannosyltransferase) [NCBI Gene 85365] {aka CDG1I, CDGIi, CMS14, CMSTA3, NET38, hALPG2}, RHOT1 (ras homolog family member T1) [NCBI Gene 55288] {aka ARHT1, MIRO-1, MIRO1}, ASH1L (ASH1 like histone lysine methyltransferase) [NCBI Gene 55870] {aka ASH1, ASH1L1, KMT2H, MRD52}, S100A6 (S100 calcium binding protein A6) [NCBI Gene 6277] {aka 2A9, 5B10, CABP, CACY, PRA, S10A6}, MYH14 (myosin heavy chain 14) [NCBI Gene 79784] {aka DFNA4, DFNA4A, FP17425, MHC16, MYH17, NMHC II-C}, COX7C (cytochrome c oxidase subunit 7C) [NCBI Gene 1350], NSF (N-ethylmaleimide sensitive factor, vesicle fusing ATPase) [NCBI Gene 4905] {aka DEE96, SEC18, SKD2}, FKBP1B (FKBP prolyl isomerase 1B) [NCBI Gene 2281] {aka FKBP12.6, FKBP1L, OTK4, PKBP1L, PPIase}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, SEPTIN7 (septin 7) [NCBI Gene 989] {aka CDC10, CDC3, NBLA02942, SEPT7, SEPT7A, Septin-7}, SUGP1 (SURP and G-patch domain containing 1) [NCBI Gene 57794] {aka F23858, RBP, SF4}, TBCD (tubulin folding cofactor D) [NCBI Gene 6904] {aka PEBAT, SSD-1, tfcD}, UBE3A (ubiquitin protein ligase E3A) [NCBI Gene 7337] {aka ANCR, AS, E6-AP, EPVE6AP, HPVE6A, PIX1}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, RAB7B (RAB7B, member RAS oncogene family) [NCBI Gene 338382] {aka RAB7}, ATP5 (delta subunit of Mt ATP synthase) [NCBI Gene 831186] {aka delta subunit of Mt ATP synthase}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, LAMP1 (lysosome associated membrane protein 1) [NCBI Gene 3916] {aka CD107a, LAMPA, LGP120}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, SYNJ2 (synaptojanin 2) [NCBI Gene 8871] {aka INPP5H}, MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}, CNBP (CCHC-type zinc finger nucleic acid binding protein) [NCBI Gene 7555] {aka CNBP1, DM2, PROMM, RNF163, ZCCHC22, ZNF9}, RAB5A (RAB5A, member RAS oncogene family) [NCBI Gene 5868] {aka RAB5}, EEA1 (early endosome antigen 1) [NCBI Gene 8411] {aka MST105, MSTP105, ZFYVE2}, TOMM20 (translocase of outer mitochondrial membrane 20) [NCBI Gene 9804] {aka MAS20, MOM19, TOM20}
- **Diseases:** fungal (MESH:D009181), ALS (MESH:D000690), neurological disorders (MESH:D009461), cardiovascular disorders (MESH:D002318), smut disease (MESH:D004194), neuronal disease (MESH:D016472), cancer (MESH:D009369), abnormal vision (MESH:D014786), ETC (MESH:D028361), BORC (MESH:D000386), neurogenerative disorders (MESH:D001750), Charcot-Marie-Tooth type 2B (MESH:C537989)
- **Chemicals:** m6A (MESH:C005955), ATP (MESH:D000255), oligomycin (MESH:D009840), N6-methyladenosine (MESH:C010223), poly(A) (MESH:D011061), Ca2+ (-), PI3P (MESH:C055525), PI(3,5)P2 (MESH:C106336), GTP (MESH:D006160), lipid (MESH:D008055), calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606], Sordaria macrospora (species) [taxon 5147], Neurospora crassa (species) [taxon 5141], Drosophila melanogaster (fruit fly, species) [taxon 7227], Rattus norvegicus (brown rat, species) [taxon 10116], Mycosarcoma maydis (corn smut, species) [taxon 5270], Xenopus laevis (African clawed frog, species) [taxon 8355], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Melanogaster (genus) [taxon 80614], Danio rerio (leopard danio, species) [taxon 7955]
- **Cell lines:** U. maydis — Homo sapiens (Human), Fibrosarcoma, Cancer cell line (CVCL_A3FC)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12852828/full.md

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Source: https://tomesphere.com/paper/PMC12852828