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RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether

Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules “hi...

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Autores principales: Liao, Ya-Cheng, Fernandopulle, Michael S., Wang, Guozhen, Choi, Heejun, Hao, Ling, Drerup, Catherine M., Patel, Rajan, Qamar, Seema, Nixon-Abell, Jonathon, Shen, Yi, Meadows, William, Vendruscolo, Michele, Knowles, Tuomas P.J., Nelson, Matthew, Czekalska, Magdalena A., Musteikyte, Greta, Gachechiladze, Mariam A., Stephens, Christina A., Pasolli, H. Amalia, Forrest, Lucy R., St George-Hyslop, Peter, Lippincott-Schwartz, Jennifer, Ward, Michael E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890474/
https://www.ncbi.nlm.nih.gov/pubmed/31539493
http://dx.doi.org/10.1016/j.cell.2019.08.050
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author Liao, Ya-Cheng
Fernandopulle, Michael S.
Wang, Guozhen
Choi, Heejun
Hao, Ling
Drerup, Catherine M.
Patel, Rajan
Qamar, Seema
Nixon-Abell, Jonathon
Shen, Yi
Meadows, William
Vendruscolo, Michele
Knowles, Tuomas P.J.
Nelson, Matthew
Czekalska, Magdalena A.
Musteikyte, Greta
Gachechiladze, Mariam A.
Stephens, Christina A.
Pasolli, H. Amalia
Forrest, Lucy R.
St George-Hyslop, Peter
Lippincott-Schwartz, Jennifer
Ward, Michael E.
author_facet Liao, Ya-Cheng
Fernandopulle, Michael S.
Wang, Guozhen
Choi, Heejun
Hao, Ling
Drerup, Catherine M.
Patel, Rajan
Qamar, Seema
Nixon-Abell, Jonathon
Shen, Yi
Meadows, William
Vendruscolo, Michele
Knowles, Tuomas P.J.
Nelson, Matthew
Czekalska, Magdalena A.
Musteikyte, Greta
Gachechiladze, Mariam A.
Stephens, Christina A.
Pasolli, H. Amalia
Forrest, Lucy R.
St George-Hyslop, Peter
Lippincott-Schwartz, Jennifer
Ward, Michael E.
author_sort Liao, Ya-Cheng
collection PubMed
description Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules “hitchhike” on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether between RNA granules and lysosomes. ANXA11 possesses an N-terminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. RNA granule transport requires ANXA11, and amyotrophic lateral sclerosis (ALS)-associated mutations in ANXA11 impair RNA granule transport by disrupting their interactions with lysosomes. Thus, ANXA11 mediates neuronal RNA transport by tethering RNA granules to actively-transported lysosomes, performing a critical cellular function that is disrupted in ALS.
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spelling pubmed-68904742020-03-03 RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether Liao, Ya-Cheng Fernandopulle, Michael S. Wang, Guozhen Choi, Heejun Hao, Ling Drerup, Catherine M. Patel, Rajan Qamar, Seema Nixon-Abell, Jonathon Shen, Yi Meadows, William Vendruscolo, Michele Knowles, Tuomas P.J. Nelson, Matthew Czekalska, Magdalena A. Musteikyte, Greta Gachechiladze, Mariam A. Stephens, Christina A. Pasolli, H. Amalia Forrest, Lucy R. St George-Hyslop, Peter Lippincott-Schwartz, Jennifer Ward, Michael E. Cell Article Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules “hitchhike” on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether between RNA granules and lysosomes. ANXA11 possesses an N-terminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. RNA granule transport requires ANXA11, and amyotrophic lateral sclerosis (ALS)-associated mutations in ANXA11 impair RNA granule transport by disrupting their interactions with lysosomes. Thus, ANXA11 mediates neuronal RNA transport by tethering RNA granules to actively-transported lysosomes, performing a critical cellular function that is disrupted in ALS. Cell Press 2019-09-19 /pmc/articles/PMC6890474/ /pubmed/31539493 http://dx.doi.org/10.1016/j.cell.2019.08.050 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liao, Ya-Cheng
Fernandopulle, Michael S.
Wang, Guozhen
Choi, Heejun
Hao, Ling
Drerup, Catherine M.
Patel, Rajan
Qamar, Seema
Nixon-Abell, Jonathon
Shen, Yi
Meadows, William
Vendruscolo, Michele
Knowles, Tuomas P.J.
Nelson, Matthew
Czekalska, Magdalena A.
Musteikyte, Greta
Gachechiladze, Mariam A.
Stephens, Christina A.
Pasolli, H. Amalia
Forrest, Lucy R.
St George-Hyslop, Peter
Lippincott-Schwartz, Jennifer
Ward, Michael E.
RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title_full RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title_fullStr RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title_full_unstemmed RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title_short RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
title_sort rna granules hitchhike on lysosomes for long-distance transport, using annexin a11 as a molecular tether
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890474/
https://www.ncbi.nlm.nih.gov/pubmed/31539493
http://dx.doi.org/10.1016/j.cell.2019.08.050
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