bims-nucpor 2022-10-09 papers

Issue of 2022‒10‒09
four papers selected by
Sara Mingu
Johannes Gutenberg University

Nat Commun. 2022 Oct 06. 13(1): 5881

RNA export through the nuclear pore complex is directional.

Asaf Ashkenazy-Titelman, Mohammad Khaled Atrash, Alon Boocholez, Noa Kinor, Yaron Shav-Tal.

The changes occurring in mRNA organization during nucleo-cytoplasmic transport and export, are not well understood. Moreover, directionality of mRNA passage through the nuclear pore complex (NPC) has not been examined within individual NPCs. Here we find that an mRNP is compact during nucleoplasmic travels compared to a more open structure after transcription and at the nuclear periphery. Compaction levels of nuclear transcripts can be modulated by varying levels of SR proteins and by changing genome organization. Nuclear mRNPs are mostly rod-shaped with distant 5'/3'-ends, although for some, the ends are in proximity. The latter is more abundant in the cytoplasm and can be modified by translation inhibition. mRNAs and lncRNAs exiting the NPC exhibit predominant 5'-first export. In some cases, several adjacent NPCs are engaged in export of the same mRNA suggesting 'gene gating'. Altogether, we show that the mRNP is a flexible structure during travels, with 5'-directionality during export.

DOI: https://doi.org/10.1038/s41467-022-33572-7

J Mol Cell Biol. 2022 Oct 03. pii: mjac056. [Epub ahead of print]

Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis.

Hameed Akbar, Jun Cao, Dongmei Wang, Xiao Yuan, Manjuan Zhang, Saravanakumar Muthusamy, Xiaoyu Song, Xu Liu, Felix Aikhionbare, Xuebiao Yao, Xinjiao Gao, Xing Liu.

Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. In eukaryotic cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Although a list of mitotic kinases has been implicated in NEBD, how they coordinate their activity to dissolve nuclear envelope and protein machinery such as nuclear pore complexes was unclear. Here, we identified a regulatory mechanism in which Nup62 is acetylated by TIP60 in human cell division. Nup62 is a novel substrate of TIP60, and the acetylation of Lys432 by TIP60 dissolves nucleoporin Nup62-Nup58-Nup54 complex during entry into mitosis. Importantly, this acetylation-elicited remodeling of nucleoporin complex promotes the distribution of Nup62 to mitotic spindle, which is indispensable for orchestrating correct spindle orientation. Moreover, suppression of Nup62 perturbs accurate chromosome segregation during mitosis. These results establish a previously uncharacterized regulatory mechanism in which TIP60-elicited nucleoporin dynamics promotes chromosome segregation in mitosis.

Keywords: Nup62; TIP60; acetylation; mitosis; spindle

DOI: https://doi.org/10.1093/jmcb/mjac056

Dev Biol. 2022 Oct 04. pii: S0012-1606(22)00181-6. [Epub ahead of print]

RanBP1 plays an essential role in directed migration of neural crest cells during development.

Elias H Barriga, Delan N Alasaadi, Chiara Mencarelli, Roberto Mayor, Franck Pichaud.

Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.

Keywords: Cell migration; LKB1; Neural crest cells; Nucleocytoplasmic transport; RanBP1

DOI: https://doi.org/10.1016/j.ydbio.2022.09.010

Nat Commun. 2022 Oct 06. 13(1): 5887

Differential nuclear import sets the timing of protein access to the embryonic genome.

Thao Nguyen, Eli J Costa, Tim Deibert, Jose Reyes, Felix C Keber, Miroslav Tomschik, Michael Stadlmeier, Meera Gupta, Chirag K Kumar, Edward R Cruz, Amanda Amodeo, Jesse C Gatlin, Martin Wühr.

The development of a fertilized egg to an embryo requires the proper temporal control of gene expression. During cell differentiation, timing is often controlled via cascades of transcription factors (TFs). However, in early development, transcription is often inactive, and many TF levels stay constant, suggesting that alternative mechanisms govern the observed rapid and ordered onset of gene expression. Here, we find that in early embryonic development access of maternally deposited nuclear proteins to the genome is temporally ordered via importin affinities, thereby timing the expression of downstream targets. We quantify changes in the nuclear proteome during early development and find that nuclear proteins, such as TFs and RNA polymerases, enter the nucleus sequentially. Moreover, we find that the timing of nuclear proteins' access to the genome corresponds to the timing of downstream gene activation. We show that the affinity of proteins to importin is a major determinant in the timing of protein entry into embryonic nuclei. Thus, we propose a mechanism by which embryos encode the timing of gene expression in early development via biochemical affinities. This process could be critical for embryos to organize themselves before deploying the regulatory cascades that control cell identities.

DOI: https://doi.org/10.1038/s41467-022-33429-z