TY - JOUR
T1 - mRNA recognition and packaging by the human transcription–export complex
AU - Pacheco-Fiallos, Belén
AU - Vorländer, Matthias K.
AU - Riabov-Bassat, Daria
AU - Fin, Laura
AU - O’Reilly, Francis J.
AU - Ayala, Farja I.
AU - Schellhaas, Ulla
AU - Rappsilber, Juri
AU - Plaschka, Clemens
N1 - Funding Information:
We thank members of the Plaschka Group for their help and discussions; staff at the Protein Technologies Facility at the Vienna BioCenter Core Facilities (VBCF), a member of the Vienna BioCenter (VBC), for assistance with protein production; staff at the VBCF Electron Microscopy Facility, in particular T. Heuser and H. Kotisch, for support, data collection and maintaining facilities; V.-V. Hodirnau at the Institute of Science and Technology Austria EM facility for cryo-EM data collection; K. M. Davies and V. Vogirala for data collection at eBIC (Diamond Light Source) and I. Grishkovskaya for assistance; R. Zimmermann and his team for computational support; K. Mechtler and his team for MS; staff at the in-house Molecular Biology Service for reagents; staff at the VBCF Next Generation Sequencing Facility for Illumina sequencing; J. Ahel for help with scripting and M. Novatchkova for help with the tSNE analysis; members of the Haselbach and Balzarotti laboratories (IMP Vienna) for sharing reagents; S. Falk and J. Zuber for sharing reagents and expertise; A. Phillip for help with mammalian cell culture; the UCSF ChimeraX team, especially T. Goddard, for implementing new functions for tomography analysis; S. Ameres, C. Bernecky, J. Brennecke, L. Cochella, A. Pauli and A. Stark for discussions; and S. Ameres, C. Bernecky, J. Brennecke, D. Gerlich, E. Nogales, A. Pauli, J.-M. Peters, G. Riddihough (Life Science Editors) and A. Stark for critical reading of the manuscript. M.K.V. was supported by an EMBO Postdoctoral Fellowship. D.R.-B. was supported by a Marie Sklodowska-Curie fellowship (101028744). J.R. was supported by core funding from the Wellcome Trust (203149). C.P. was supported by Boehringer Ingelheim and the European Research Council (ERC-2020-STG 949081 RNApaxport). For the purpose of open access, the author has applied for a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Funding Information:
We thank members of the Plaschka Group for their help and discussions; staff at the Protein Technologies Facility at the Vienna BioCenter Core Facilities (VBCF), a member of the Vienna BioCenter (VBC), for assistance with protein production; staff at the VBCF Electron Microscopy Facility, in particular T. Heuser and H. Kotisch, for support, data collection and maintaining facilities; V.-V. Hodirnau at the Institute of Science and Technology Austria EM facility for cryo-EM data collection; K. M. Davies and V. Vogirala for data collection at eBIC (Diamond Light Source) and I. Grishkovskaya for assistance; R. Zimmermann and his team for computational support; K. Mechtler and his team for MS; staff at the in-house Molecular Biology Service for reagents; staff at the VBCF Next Generation Sequencing Facility for Illumina sequencing; J. Ahel for help with scripting and M. Novatchkova for help with the tSNE analysis; members of the Haselbach and Balzarotti laboratories (IMP Vienna) for sharing reagents; S. Falk and J. Zuber for sharing reagents and expertise; A. Phillip for help with mammalian cell culture; the UCSF ChimeraX team, especially T. Goddard, for implementing new functions for tomography analysis; S. Ameres, C. Bernecky, J. Brennecke, L. Cochella, A. Pauli and A. Stark for discussions; and S. Ameres, C. Bernecky, J. Brennecke, D. Gerlich, E. Nogales, A. Pauli, J.-M. Peters, G. Riddihough (Life Science Editors) and A. Stark for critical reading of the manuscript. M.K.V. was supported by an EMBO Postdoctoral Fellowship. D.R.-B. was supported by a Marie Sklodowska-Curie fellowship (101028744). J.R. was supported by core funding from the Wellcome Trust (203149). C.P. was supported by Boehringer Ingelheim and the European Research Council (ERC-2020-STG 949081 RNApaxport). For the purpose of open access, the author has applied for a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/4/27
Y1 - 2023/4/27
N2 - Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription–export complex (TREX) for nuclear export1,2. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood3. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.
AB - Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription–export complex (TREX) for nuclear export1,2. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood3. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.
U2 - 10.1038/s41586-023-05904-0
DO - 10.1038/s41586-023-05904-0
M3 - Article
C2 - 37020021
AN - SCOPUS:85151496239
SN - 0028-0836
VL - 616
SP - 828
EP - 835
JO - Nature
JF - Nature
IS - 7958
M1 - 616
ER -