H2020Individual fellowship2018–2020

WISDOM · The autonomous floral pathway: a WIndow to Study the tight link between non-coDing RNA and chrOMatin regulation

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-04-01 → 2020-03-31
EU contribution
€195,455
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

The autonomous floral pathway: a WIndow to Study the tight link between non-coDing RNA and chrOMatin regulation

Problem being addressed: RNA-mediated chromatin regulation is central to gene expression in many organisms. However, the mechanisms by which RNA influences the local chromatin environment are still poorly understood. The work supported by my MSCA fellowship showed how RNA 3’ processing factors promote proximal polyadenylation of an antisense transcript and how this physically links with chromatin modifiers FLD/LD/SDG26. Why important for society: Both long and short non-coding chromatin-associated RNA transcripts have emerged as key regulators of the chromatin environment. Detailed mechanisms of how 21-24 nucleotide RNAs initiate and maintain heterochromatin have been elucidated. However, less is understood about the mechanisms linking long non-coding RNA, chromatin regulation and transcription. The work supported by my MSCA fellowship will reveal any further parallels between COOLAIR and Xist function, thus elaborating the evolutionary understanding of RNA-mediated chromatin silencing by the research community. Overall objectives: This fellowship addressed the following four interconnected questions: 1. Does the FCA/FY-mediated repression of FLC depend on SDG26? 2. What are the primary chromatin changes delivered by FLD/SDG26? 3. How does the chromatin environment delivered by FLD/SDG26 repress transcription? 4. What is the link between FCA and FLD/SDG26?

Data: CORDIS, © European Union

Project objective

My Fellowship will explore the interconnection between non-coding RNA and chromatin regulation. Building on a detailed mechanistic base, I will capitalize on the recent proteomic identification of a stable complex FLD/SDG26 by my host lab, which plays a central role in the co-transcriptional silencing of the Arabidopsis floral repressor locus FLC. This protein complex is central to a mechanism determining the quantitative expression level of FLC, and thus the reproductive strategy of the plant. However, these activities also regulate many other targets in the Arabidopsis genome and the conserved nature of the components suggests the deeper understanding gained from this study will be important generally across all eukaryotes. FLD is a histone demethylase with specificity for H3K4; SDG26 is a SET domain protein likely to methylate histones and other proteins, but whose specificity is currently unknown. The splicing and alternative processing of FLC antisense non-coding transcript, COOLAIR, is essential for the repression of FLC transcription. However, how the processing of COOLAIR controls sense transcription remains elusive. My proposal aims to: 1) test the hypothesis that the FLD/SDG26 complex, triggered by FCA/FY-mediated proximal polyadenylation of COOLAIR, delivers a specific chromatin environment, which represses transcriptional output: and 2) explore the missing link between FCA/FY-mediated proximal polyadenylation of COOLAIR and chromatin regulation by FLD/SDG26 complex. My proposal involves interconnections between genetics, biochemistry and molecular biology, enabling me to develop a broader experimental skillset. It directly contributes to the action’s goals to: improve my creative potential and competences through international mobility and advanced training in technical and transferable skills; enhance collaborative and contact networks for both myself and my host lab through academic and public engagement; and drive substantial career development.

Original text from CORDIS.

Participants

Links

Data: CORDIS, © European Union