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H2020Individual fellowship2021–2023

Rn7SKmod · Impact of RNA modifications on neuronal fate

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-07-01 → 2023-06-30
EU contribution
€162,806
Participants
1
Scheme
MSCA-IF

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Results in brief

Impact of RNA modifications on neuronal fate

The project aimed to investigate the functional roles of RNA modifications within the non-coding RNA Rn7sk, with a specific focus on their involvement in regulating neural fate decisions. The objectives of the project were threefold: 1. Identification and modulation of Rn7sk RNA modifications: The first objective (WP 1) was to comprehensively identify all RNA modifications specific to Rn7sk and subsequently examine how these modifications influence interactions between RNA and proteins. By delving into this aspect, the project sought to uncover the intricate mechanisms through which RNA modifications shape vital cellular processes. 2. Neuronal differentiation regulation: The second objective (WP 2) revolved around unraveling the mechanisms by which Rn7sk contributes to the regulation of neuronal differentiation in mouse embryonic stem cells (mESCs). This aspect of the study aimed to shed light on the pivotal role of Rn7sk in steering the development of neural cells and pathways. 3. Transcriptional impact of Rn7sk-deletion: The third objective (WP 3) involved analyzing the transcriptional effects arising from the deletion of Rn7sk within the forebrain. By examining the changes in gene expression patterns resulting from this deletion, the project aimed to provide insights into the broader consequences of Rn7sk on brain development and function. The significance of this project extended to society at large due to its potential to uncover crucial insights into brain development and function. By understanding how RNA modifications influence neural fate decisions, the research had the potential to offer groundbreaking perspectives on neurodevelopmental disorders. These findings could lead to the identification of novel therapeutic targets, thereby paving the way for clinical interventions that address the complexities of such disorders. In conclusion, this MSCA European individual postdoc fellowship centered around investigating the impact of RNA modifications within Rn7sk on neural fate decisions. Through comprehensive exploration and analysis, the project aimed to contribute to the understanding of brain development and its potential applications in tackling neurodevelopmental disorders. The insights gained from the project have the potential to open new avenues for therapeutic interventions and offer hope for individuals facing such challenges.

Data: CORDIS, © European Union

Project objective

The Epitranscriptome is the assembly of over 170 chemical RNA modifications that play fundamental roles in the majority of cellular processes. RNA modifying enzymes and proper control of neuronal cell fate are essential for brain development and dysfunction in any of these processes results in severe neurodevelopmental disorders. To date, the role of non-coding RNAs (ncRNAs) as key regulators of sophisticated molecular pathways is becoming increasingly clear. A key regulatory ncRNA that modulates the transcriptional output of RNA polymerase II is Rn7sk. Other abundant ncRNAs, like transfer RNAs and ribosomal RNAs, are highly modified; yet the modifications occurring in Rn7sk are largely unknown. In this proposal, I aim to investigate the Rn7sk RNA modification status and the impact of these modifications on neuronal cell fate and brain development. To accomplish this, I will; i) Characterize Rn7sk RNA modifications using a highly sensitive RNA mass spectrometry approach and evaluate the impact of selected modifications in recruiting protein binding partners using stable isotope labelling by amino acids in cell culture (SILAC) based mass spectrometry; ii) Determine the biological function of selected Rn7sk modifications during neuronal differentiation using genetically manipulated embryonic cell lines; iii) Investigate the role of Rn7sk during brain development using genome-wide sequencing technologies and a forebrain-specific Rn7sk knock-out mouse model. Results stemming from this project will reveal several novel aspects about how neuronal fate is controlled by tiny RNA modifications. My ultimate ambition is to establish my own laboratory and become an independent research leader in the field of Epitranscriptomics. This proposal, with the support from the experienced Prof Frye and the excellent host institute, DKFZ, is key for me to reach my goal.

Original text from CORDIS.

Participants

  • DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG · HeidelbergCoordinatorGermany

Links

Data: CORDIS, © European Union