Nature Cell Biology, volume 24, issue 10, pages 1541-1557

Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells

Larionova Tatyana D ¹

Bastola Soniya ²

Aksinina Tatiana E ¹

Anufrieva Ksenia S. ^{3, 4}

Wang Jia ⁵

Shender Victoria O ^{1, 3, 4}

Andreev Dmitry E ^{1, 6}

Kovalenko Tatiana F ¹

Arapidi Georgij P ^{1, 3, 4}

Shnaider Polina V. ^{3, 4}

Kazakova Anastasia N. ⁴

Latyshev Yaroslav A ⁷

Tatarskiy Victor V. ⁸

Shtil Alexander A. ⁹

Moreau Pascale ¹⁰

Giraud Francis ¹⁰

Li Chaoxi ¹¹

Wang Yichan ⁵

Rubtsova Maria P ^{1, 6}

Dontsova Olga A. ^{1, 6, 12}

Condro Michael ²

Ellingson Benjamin M. ^{13, 14, 15, 16}

Shakhparonov Mikhail I ¹

Kornblum Harley I. ¹⁷

Nakano Ichiro ¹⁸

Pavlyukov Marat S ^{1, 19}

Hide authors affiliations Show authors affiliations: 19 affiliations

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation |

Department of Bioengineering, University of California Los Angeles, Los Angeles, USA |

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, Russian Federation |

⁴

Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical and Biological Agency, Moscow, Russian Federation |

⁵

Department of Neurosurgery, Centre of Brain Science, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China |

⁶

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation |

⁷

N.N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Health of the Russian Federation, Moscow, Russian Federation |

⁸

Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian Federation |

⁹

Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation |

¹⁰

Institute of Chemistry of Clermont-Ferrand, CNRS, Université Clermont Auvergne, Clermont-Ferrand, France |

¹¹

Department of Neurosurgery, School of Medicine and O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA |

¹²

Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation |

¹³

Department of Neurosurgery, University of California Los Angeles, Los Angeles, USA |

¹⁴

Department of Psychiatry, University of California Los Angeles, Los Angeles, USA |

¹⁵

Department of Radiological Sciences, University of California Los Angeles, Los Angeles, USA |

¹⁶

Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, University of California Los Angeles, Los Angeles, USA |

¹⁷

Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA |

¹⁸

Department of Neurosurgery, Medical Institute of Hokuto, Hokkaido, Japan |

¹⁹

Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain |

Publication type: Journal Article

Publication date: 2022-10-03

Springer Nature

Journal: Nature Cell Biology

Quartile SCImago

Quartile WOS

Impact factor: 21.3

ISSN: 14657392, 14764679

DOI: 10.1038/s41556-022-00994-w

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Cell Biology

Abstract

Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy. Larionova et al. identify a mechanism by which acidification of the tumour microenvironment within the glioblastoma core induces the generation of an alternative splice isoform of ribosomal protein RPL22L1, which regulates cell stemness and increases tumour heterogeneity.

By date By citations

Citations by journals

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Cell Reports Medicine	Cell Reports Medicine, 1, 4.55% Cell Reports Medicine 1 publication, 4.55%
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Toxins	Toxins, 1, 4.55% Toxins 1 publication, 4.55%
Journal of Clinical Investigation	Journal of Clinical Investigation, 1, 4.55% Journal of Clinical Investigation 1 publication, 4.55%
Philosophical Transactions of the Royal Society B: Biological Sciences	Philosophical Transactions of the Royal Society B: Biological Sciences, 1, 4.55% Philosophical Transactions of the Royal Society B: Biological Sciences 1 publication, 4.55%
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Citations by publishers

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Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 6, 27.27% Multidisciplinary Digital Publishing Institute (MDPI) 6 publications, 27.27%
Springer Nature	Springer Nature, 4, 18.18% Springer Nature 4 publications, 18.18%
Elsevier	Elsevier, 3, 13.64% Elsevier 3 publications, 13.64%
Oxford University Press	Oxford University Press, 2, 9.09% Oxford University Press 2 publications, 9.09%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 4.55% American Chemical Society (ACS) 1 publication, 4.55%
Pleiades Publishing	Pleiades Publishing, 1, 4.55% Pleiades Publishing 1 publication, 4.55%
Wiley	Wiley, 1, 4.55% Wiley 1 publication, 4.55%
American Society for Clinical Investigation	American Society for Clinical Investigation, 1, 4.55% American Society for Clinical Investigation 1 publication, 4.55%
The Royal Society	The Royal Society, 1, 4.55% The Royal Society 1 publication, 4.55%
	1 2 3 4 5 6

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Larionova T. D. et al. Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells // Nature Cell Biology. 2022. Vol. 24. No. 10. pp. 1541-1557.

GOST all authors (up to 50) Copy

Larionova T. D., Bastola S., Aksinina T. E., Anufrieva K. S., Wang J., Shender V. O., Andreev D. E., Kovalenko T. F., Arapidi G. P., Shnaider P. V., Kazakova A. N., Latyshev Y. A., Tatarskiy V. V., Shtil A. A., Moreau P., Giraud F., Li C., Wang Y., Rubtsova M. P., Dontsova O. A., Condro M., Ellingson B. M., Shakhparonov M. I., Kornblum H. I., Nakano I., Pavlyukov M. S. Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells // Nature Cell Biology. 2022. Vol. 24. No. 10. pp. 1541-1557.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/s41556-022-00994-w

UR - https://doi.org/10.1038%2Fs41556-022-00994-w

TI - Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells

T2 - Nature Cell Biology

AU - Larionova, Tatyana D

AU - Bastola, Soniya

AU - Aksinina, Tatiana E

AU - Anufrieva, Ksenia S.

AU - Wang, Jia

AU - Shender, Victoria O

AU - Andreev, Dmitry E

AU - Kovalenko, Tatiana F

AU - Arapidi, Georgij P

AU - Shnaider, Polina V.

AU - Kazakova, Anastasia N.

AU - Latyshev, Yaroslav A

AU - Tatarskiy, Victor V.

AU - Shtil, Alexander A.

AU - Moreau, Pascale

AU - Giraud, Francis

AU - Li, Chaoxi

AU - Wang, Yichan

AU - Rubtsova, Maria P

AU - Dontsova, Olga A.

AU - Condro, Michael

AU - Ellingson, Benjamin M.

AU - Shakhparonov, Mikhail I

AU - Kornblum, Harley I.

AU - Nakano, Ichiro

AU - Pavlyukov, Marat S

PY - 2022

DA - 2022/10/03 00:00:00

PB - Springer Nature

SP - 1541-1557

IS - 10

VL - 24

SN - 1465-7392

SN - 1476-4679

ER -

BibTex |

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BibTex Copy

@article{2022_Larionova,

author = {Tatyana D Larionova and Soniya Bastola and Tatiana E Aksinina and Ksenia S. Anufrieva and Jia Wang and Victoria O Shender and Dmitry E Andreev and Tatiana F Kovalenko and Georgij P Arapidi and Polina V. Shnaider and Anastasia N. Kazakova and Yaroslav A Latyshev and Victor V. Tatarskiy and Alexander A. Shtil and Pascale Moreau and Francis Giraud and Chaoxi Li and Yichan Wang and Maria P Rubtsova and Olga A. Dontsova and Michael Condro and Benjamin M. Ellingson and Mikhail I Shakhparonov and Harley I. Kornblum and Ichiro Nakano and Marat S Pavlyukov},

title = {Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells},

journal = {Nature Cell Biology},

year = {2022},

volume = {24},

publisher = {Springer Nature},

month = {oct},

url = {https://doi.org/10.1038%2Fs41556-022-00994-w},

number = {10},

pages = {1541--1557},

doi = {10.1038/s41556-022-00994-w}

}

MLA

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MLA Copy

Larionova, Tatyana D., et al. “Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.” Nature Cell Biology, vol. 24, no. 10, Oct. 2022, pp. 1541-1557. https://doi.org/10.1038%2Fs41556-022-00994-w.

Found error?

Publisher

Springer Nature

Journal

Nature Cell Biology

Quartile SCImago

Quartile WOS

Impact factor

21.3

ISSN

14657392 (Print)
14764679 (Electronic)

Labs

Laboratory of Nucleoprotein Chemistry, Department of Chemistry of Natural Compounds, Faculty of Chemistry

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