The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
RNA localization and co‐translational interactions control RAB13 GTPase function and cell migration
Open accessPublished version of a preprint
Abstract
Numerous RNAs exhibit specific distribution patterns in mammalian cells. However, the functional and mechanistic consequences are relatively unknown. Here, we investigate the functional role of RNA localization at cellular protrusions of migrating mesenchymal cells, using as a model the RAB13 RNA, which encodes a GTPase important for vesicle‐mediated membrane trafficking. While RAB13 RNA is enriched at peripheral protrusions, the expressed protein is concentrated perinuclearly. By specifically preventing RAB13 RNA localization, we show that peripheral RAB13 translation is not important for the overall distribution of the RAB13 protein or its ability to associate with membranes, but is required for full activation of the GTPase and for efficient cell migration. RAB13 translation leads to a co‐translational association of nascent RAB13 with the exchange factor RABIF. Our results indicate that RAB13‐RABIF association at the periphery is required for directing RAB13 GTPase activity to promote cell migration. Thus, translation of RAB13 in specific subcellular environments imparts the protein with distinct properties and highlights a means of controlling protein function through local RNA translation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization
Berkovits, B. D., & Mayr, C. (2015) · Nature · doi:10.1038/nature14321 · Cited by 474
Flagged first, then by citations
Research works printed but not linked: 58
- Barry DJ, Durkin CH, Abella JV, Way M (2015) Open source software for quantification of cell migration, protrusions, and fluorescence intensities. J Cell Biol 209: 163–180 · DOI
- Basu SK, Malik R, Huggins CJ, Lee S, Sebastian T, Sakchaisri K, Quinones OA, Alvord WG, Johnson PF (2011) 3′UTR elements inhibit Ras‐induced C/EBPbeta post‐translational activation and senescence in tumour cells. EMBO J 30: 3714–3728 · DOI
- Besse F, Ephrussi A (2008) Translational control of localized mRNAs: restricting protein synthesis in space and time. Nat Rev Mol Cell Biol 9: 971–980 · DOI
- Boisvert FM, Ahmad Y, Gierlinski M, Charriere F, Lamont D, Scott M, Barton G, Lamond AI (2012) A quantitative spatial proteomics analysis of proteome turnover in human cells. Mol Cell Proteomics 11: M111.011429 · DOI · Paper page
- Burton J, Roberts D, Montaldi M, Novick P, De Camilli P (1993) A mammalian guanine‐nucleotide‐releasing protein enhances function of yeast secretory protein Sec4. Nature 361: 464–467 · DOI
- Burton JL, Burns ME, Gatti E, Augustine GJ, De Camilli P (1994) Specific interactions of Mss4 with members of the Rab GTPase subfamily. EMBO J 13: 5547–5558 · DOI
- Buxbaum AR, Haimovich G, Singer RH (2015) In the right place at the right time: visualizing and understanding mRNA localization. Nat Rev Mol Cell Biol 16: 95–109 · DOI
- Cagnetta R, Frese CK, Shigeoka T, Krijgsveld J, Holt CE (2018) Rapid cue‐specific remodeling of the nascent axonal proteome. Neuron 99: 29–46 · DOI
- Colak D, Ji SJ, Porse BT, Jaffrey SR (2013) Regulation of axon guidance by compartmentalized nonsense‐mediated mRNA decay. Cell 153: 1252–1265 · DOI
- Costa G, Bradbury J, Tarannum N, Herbert SP (2020) RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis. EMBO J 39: e106003 · DOI
- Fazal FM, Han S, Parker KR, Kaewsapsak P, Xu J, Boettiger AN, Chang HY, Ting AY (2019) Atlas of subcellular RNA localization revealed by APEX‐Seq. Cell 178: 473–490 · DOI
- Feltrin D, Fusco L, Witte H, Moretti F, Martin K, Letzelter M, Fluri E, Scheiffele P, Pertz O (2012) Growth cone MKK7 mRNA targeting regulates MAP1b‐dependent microtubule bundling to control neurite elongation. PLoS Biol 10: e1001439 · DOI
- Gloge F, Becker AH, Kramer G, Bukau B (2014) Co‐translational mechanisms of protein maturation. Curr Opin Struct Biol 24: 24–33 · DOI
- Gorelik R, Gautreau A (2014) Quantitative and unbiased analysis of directional persistence in cell migration. Nat Protoc 9: 1931–1943 · DOI
- Gulbranson DR, Davis EM, Demmitt BA, Ouyang Y, Ye Y, Yu H, Shen J (2017) RABIF/MSS4 is a Rab‐stabilizing holdase chaperone required for GLUT4 exocytosis. Proc Natl Acad Sci USA 114: E8224–E8233 · DOI · Paper page
- Havens MA, Hastings ML (2016) Splice‐switching antisense oligonucleotides as therapeutic drugs. Nucleic Acids Res 44: 6549–6563 · DOI
- Holt CE, Martin KC, Schuman EM (2019) Local translation in neurons: visualization and function. Nat Struct Mol Biol 26: 557–566 · DOI
- Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, Krainer AR (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24: 1634–1644 · DOI
- Huttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X, Bassell GJ, Condeelis J, Singer RH (2005) Spatial regulation of beta‐actin translation by Src‐dependent phosphorylation of ZBP1. Nature 438: 512–515 · DOI
- Ioannou MS, Bell ES, Girard M, Chaineau M, Hamlin JN, Daubaras M, Monast A, Park M, Hodgson L, McPherson PS (2015) DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior. J Cell Biol 208: 629–648 · DOI
- Ioannou MS, McPherson PS (2016) Regulation of cancer cell behavior by the small GTPase Rab13. J Biol Chem 291: 9929–9937 · DOI
- Jung H, Gkogkas CG, Sonenberg N, Holt CE (2014) Remote control of gene function by local translation. Cell 157: 26–40 · DOI
- Kohler K, Louvard D, Zahraoui A (2004) Rab13 regulates PKA signaling during tight junction assembly. J Cell Biol 165: 175–180 · DOI
- Koppers M, Cagnetta R, Shigeoka T, Wunderlich LC, Vallejo‐Ramirez P, Qiaojin Lin J, Zhao S, Jakobs MA, Dwivedy A, Minett MS et al (2019) Receptor‐specific interactome as a hub for rapid cue‐induced selective translation in axons. Elife 8: e48718 · DOI
- Lee SH, Mayr C (2019) Gain of additional BIRC3 protein functions through 3′‐UTR‐mediated protein complex formation. Mol Cell 74: 701–712 · DOI
- Lentz JJ, Jodelka FM, Hinrich AJ, McCaffrey KE, Farris HE, Spalitta MJ, Bazan NG, Duelli DM, Rigo F, Hastings ML (2013) Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness. Nat Med 19: 345–350 · DOI
- Leung KF, Baron R, Seabra MC (2006a) Thematic review series: lipid posttranslational modifications. geranylgeranylation of Rab GTPases. J Lipid Res 47: 467–475 · DOI
- Leung KM, van Horck FP, Lin AC, Allison R, Standart N, Holt CE (2006b) Asymmetrical beta‐actin mRNA translation in growth cones mediates attractive turning to netrin‐1. Nat Neurosci 9: 1247–1256 · DOI · Paper page
- Mardakheh FK, Paul A, Kumper S, Sadok A, Paterson H, McCarthy A, Yuan Y, Marshall CJ (2015) Global analysis of mRNA, translation, and protein localization: local translation is a key regulator of cell protrusions. Dev Cell 35: 344–357 · DOI
- Marzesco AM, Dunia I, Pandjaitan R, Recouvreur M, Dauzonne D, Benedetti EL, Louvard D, Zahraoui A (2002) The small GTPase Rab13 regulates assembly of functional tight junctions in epithelial cells. Mol Biol Cell 13: 1819–1831 · DOI
- Mathieson T, Franken H, Kosinski J, Kurzawa N, Zinn N, Sweetman G, Poeckel D, Ratnu VS, Schramm M, Becher I et al (2018) Systematic analysis of protein turnover in primary cells. Nat Commun 9: 689 · DOI
- Medioni C, Mowry K, Besse F (2012) Principles and roles of mRNA localization in animal development. Development 139: 3263–3276 · DOI
- Meignin C, Davis I (2010) Transmitting the message: intracellular mRNA localization. Curr Opin Cell Biol 22: 112–119 · DOI
- Mili S, Moissoglu K, Macara IG (2008) Genome‐wide screen reveals APC‐associated RNAs enriched in cell protrusions. Nature 453: 115–119 · DOI
- Miyazaki A, Sasaki T, Araki K, Ueno N, Imazumi K, Nagano F, Takahashi K, Takai Y (1994) Comparison of kinetic properties between MSS4 and Rab3A GRF GDP/GTP exchange proteins. FEBS Lett 350: 333–336 · DOI
- Moissoglu K, Yasuda K, Wang T, Chrisafis G, Mili S (2019) Translational regulation of protrusion‐localized RNAs involves silencing and clustering after transport. Elife 8: e44752 · DOI
- Morimoto S, Nishimura N, Terai T, Manabe S, Yamamoto Y, Shinahara W, Miyake H, Tashiro S, Shimada M, Sasaki T (2005) Rab13 mediates the continuous endocytic recycling of occludin to the cell surface. J Biol Chem 280: 2220–2228 · DOI
- Muller MP, Goody RS (2018) Molecular control of Rab activity by GEFs, GAPs and GDI. Small GTPases 9: 5–21 · DOI
- Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T, Katagiri K (2014) Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA‐1 to the cell surface for lymphocyte trafficking. Sci Signal 7: ra72 · DOI
- Paquin N, Chartrand P (2008) Local regulation of mRNA translation: new insights from the bud. Trends Cell Biol 18: 105–111 · DOI
- Petrie RJ, Doyle AD, Yamada KM (2009) Random versus directionally persistent cell migration. Nat Rev Mol Cell Biol 10: 538–549 · DOI
- Pfeffer SR (2017) Rab GTPases: master regulators that establish the secretory and endocytic pathways. Mol Biol Cell 28: 712–715 · DOI
- Rangaraju V, Tom Dieck S, Schuman EM (2017) Local translation in neuronal compartments: how local is local? EMBO Rep 18: 693–711 · DOI
- Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302: 1704–1709 · DOI
- Ryan GL, Watanabe N, Vavylonis D (2012) A review of models of fluctuating protrusion and retraction patterns at the leading edge of motile cells. Cytoskeleton (Hoboken) 69: 195–206 · DOI
- Sahgal P, Alanko J, Icha J, Paatero I, Hamidi H, Arjonen A, Pietila M, Rokka A, Ivaska J (2019) GGA2 and RAB13 promote activity‐dependent beta1‐integrin recycling. J Cell Sci 132: jcs233387 · DOI
- Sakane A, Abdallah AA, Nakano K, Honda K, Ikeda W, Nishikawa Y, Matsumoto M, Matsushita N, Kitamura T, Sasaki T (2012) Rab13 small G protein and junctional Rab13‐binding protein (JRAB) orchestrate actin cytoskeletal organization during epithelial junctional development. J Biol Chem 287: 42455–42468 · DOI
- Sakane A, Alamir Mahmoud Abdallah A, Nakano K, Honda K, Kitamura T, Imoto I, Matsushita N, Sasaki T (2013) Junctional Rab13‐binding protein (JRAB) regulates cell spreading via filamins. Genes Cells 18: 810–822 · DOI
- Scott RW, Crighton D, Olson MF (2011) Modeling and imaging 3‐dimensional collective cell invasion. J Vis Exp 58: 3525
- Shiber A, Doring K, Friedrich U, Klann K, Merker D, Zedan M, Tippmann F, Kramer G, Bukau B (2018) Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling. Nature 561: 268–272 · DOI
- Shieh YW, Minguez P, Bork P, Auburger JJ, Guilbride DL, Kramer G, Bukau B (2015) Operon structure and cotranslational subunit association direct protein assembly in bacteria. Science 350: 678–680 · DOI
- Stueland M, Wang T, Park HY, Mili S (2019) RDI calculator: an analysis tool to assess RNA distributions in cells. Sci Rep 9: 8267 · DOI
- Terai T, Nishimura N, Kanda I, Yasui N, Sasaki T (2006) JRAB/MICAL‐L2 is a junctional Rab13‐binding protein mediating the endocytic recycling of occludin. Mol Biol Cell 17: 2465–2475 · DOI
- Wang T, Hamilla S, Cam M, Aranda‐Espinoza H, Mili S (2017) Extracellular matrix stiffness and cell contractility control RNA localization to promote cell migration. Nat Commun 8: 896 · DOI
- Wong HH, Lin JQ, Strohl F, Roque CG, Cioni JM, Cagnetta R, Turner‐Bridger B, Laine RF, Harris WA, Kaminski CF et al (2017) RNA docking and local translation regulate site‐specific axon remodeling in vivo. Neuron 95: 852–868 · DOI
- Wu C, Agrawal S, Vasanji A, Drazba J, Sarkaria S, Xie J, Welch CM, Liu M, Anand‐Apte B, Horowitz A (2011) Rab13‐dependent trafficking of RhoA is required for directional migration and angiogenesis. J Biol Chem 286: 23511–23520 · DOI
- Yoon YJ, Wu B, Buxbaum AR, Das S, Tsai A, English BP, Grimm JB, Lavis LD, Singer RH (2016) Glutamate‐induced RNA localization and translation in neurons. Proc Natl Acad Sci USA 113: E6877–E6886
- Zappulo A, van den Bruck D, Ciolli Mattioli C, Franke V, Imami K, McShane E, Moreno‐Estelles M, Calviello L, Filipchyk A, Peguero‐Sanchez E et al (2017) RNA localization is a key determinant of neurite‐enriched proteome. Nat Commun 8: 583 · DOI
Metadata
- Authors
- Moissoglu, K., Stueland, M., Gasparski, A. N., Wang, T., Jenkins, L. M., Hastings, M. L., & Mili, S.
- Affiliations
- National Institutes of Health (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Mili, Stavroula
- Venue
- The EMBO Journal
- Published
- 2020-09-18
- Volume
- 39
- Issue
- 21
- Pages
- e104958-e104958
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC7604616
- OpenAlex
- W3087518429
- Cited by
- 43
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 14 · 2022: 6 · 2021: 7 · 2020: 3
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, public-domain)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (1ZIA BC011501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- Rab13, cell migration, GTPase activation, local translation, cell protrusions, mesenchymal cells, membrane trafficking, vesicle trafficking, subcellular protein distribution
- MeSH terms
- Animals, Cell Movement, Humans, Mesoderm, RNA, GTP Phosphohydrolases, Guanine Nucleotide Exchange Factors, rab GTP-Binding Proteins, Protein Transport, Cell Surface Extensions, NIH 3T3 Cells, Mice, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review