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Two parallel arms of the heterochronic pathway direct coordinated juvenile-to-adult transition through distinct LIN-29 isoforms

Chiara Azzi, View ORCID ProfileFlorian Aeschimann, Anca Neagu, View ORCID ProfileHelge Großhans
doi: https://doi.org/10.1101/783001
Chiara Azzi
2Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
3University of Basel, Petersplatz 1, CH-4051 Basel, Switzerland
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Florian Aeschimann
2Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
3University of Basel, Petersplatz 1, CH-4051 Basel, Switzerland
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Anca Neagu
2Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
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Helge Großhans
2Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
3University of Basel, Petersplatz 1, CH-4051 Basel, Switzerland
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  • ORCID record for Helge Großhans
  • For correspondence: helge.grosshans@fmi.ch
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Abstract

Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the timely transition from juvenile to adult is controlled by the heterochronic pathway, a regulatory cascade of conserved proteins and small RNAs. The heterochronic pathway culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of juvenile-to-adult (J/A) transition events. Here, we reveal that two LIN-29 isoforms fulfill distinct functions during the J/A transition. We show that the functional differences between the isoforms do not stem from differences in their sequences, but from their distinct spatiotemporal expression, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique lin-29 isoform expression patterns are generated by the RNA-binding protein LIN-41 for lin-29a, and the transcription factor HBL-1 for lin-29b. By regulating both HBL-1 and LIN-41, the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity. Thus, our findings reveal that a coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 26, 2019.
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Two parallel arms of the heterochronic pathway direct coordinated juvenile-to-adult transition through distinct LIN-29 isoforms
Chiara Azzi, Florian Aeschimann, Anca Neagu, Helge Großhans
bioRxiv 783001; doi: https://doi.org/10.1101/783001
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Two parallel arms of the heterochronic pathway direct coordinated juvenile-to-adult transition through distinct LIN-29 isoforms
Chiara Azzi, Florian Aeschimann, Anca Neagu, Helge Großhans
bioRxiv 783001; doi: https://doi.org/10.1101/783001

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