Departments

Šifra projekta / Project code: N1-0364

Vodja: dr. Jernej Ule

1. Vsebinski opis projekta:

Regulacija spajanja RNK molekul je osrednji del genske regulacije, zato je njeno razumevanje ključno za številna področja. Na področju zdravstvanam pomaga razumeti vzroke in potek bolezni ter razvijati učinkovitejše terapije. V zadnjih nekaj letih se je pokazalo, da imajo lahko kriptična mesta spajanja pomembno vlogo pri uravnavanju spajanja RNK in s tem izražanjagenov. Veliko takšnih kriptičnih regulacijskih mest je treba še odkriti in preučiti mehanizme njihovega delovanja. Tu se bomo osredotočili na kriptična5' mesta spajanja (d-5'ss), ki vsebujejo zaporedja 5' mest spajanja in na katera se veže spliceosom. Ocenili bomo dva hipotetična načina njihovegadelovanja. Najprej bomo poskušali določiti delež _d-5'ss, ki sestavljajo neproduktivne spliceosomske komplekse, ki tekmujejo s prepoznavanjembližnjih kanoničnih spajalnih mest. Drugič, določili bomo delež _d-5'ss, ki se razcepijo z reakcijo spajkanja, nastale RNK molekule pa so natonamenjeni razgradnji. Nazadnje bomo preučili reprezentativne primere obeh vrst d-5'ss, da bi podrobneje ocenili njune mehanizme in preučili njunvpliv na izražanje in lokalizacijo transkriptov, proizvedenih iz gostiteljskih genov na različnih stopnjah med diferenciacijo nevronov.

Regulation of RNA splicing is a central part of gene regulation, and understanding it is therefore crucial for many fields. In the medical field, it helps us understand the causes and progression of disease and develop more effective therapies. In recent years, it has been shown that cryptic splice sites can play an important role in regulating RNA splicing and thus gene expression. Many such cryptic regulatory sites remain to be discovered, and their mechanisms of action examined. Here we will focus on decoy 5’ splice sites (d-5’ss), which contain consensus sequences of 5’ splice sites and assemble some spliceosomal components. We will assess two hypothetical modes of their action. First, we will attempt to determine the proportion of d-5’ss that assemble non-productive spliceosomal complexes, which compete with recognition of nearby canonical splice sites. Second, we will determine the proportion of d-5’ss that are cleaved via a splicing reaction, but the resulting transcripts are then targeted for degradation. Finally, we will study representative examples of both types of d-5’ss to assess their mechanisms in more detail, and examine their impact on the expression and localisation of the transcripts produced from their host genes at various stages during neuronal differentiation.

Sodelujoče organizacije:

Kemijski inštitut, Ljubljana, Slovenija

Centre for Cardiovascular Surgery and Transplantation, Pekařská 53, 656 91 Brno, Czech Republic

Osnovni podatki glede financiranja:
Projekt financira ARRS v okviru cenovne kategorije C za obdobje treh let v obsegu 2172 letnimi urami za obdobje 3 let. Pričetek financiranja je 1. 3. 2024.
The project is co-financed by ARRS with 2172 annual hours of price class C for a period of 3 years. Funding starts on 1. 3. 2024.

Sestava projektne skupine s povezavami na SICRIS
Na Kemijskem inštitutu v projektni skupini sodelujejo / At the National Institute of Chemistry the project group includes:

Jernej Ule; SICRIS št. 34667
Urška Janjoš; SICRIS št. 55058
Klara Hodnik; SICRIS št. 54867

2. Faze projekta in njihova realizacija

WP1. Karakterizacija d-5'ss, pri katerih pride do nepopolnega spajanja, po celotnem transkriptomu
WP2. Opredelitev regulativnih mehanizmov na specifičnih d-5'ss 

WP1. Transcriptome-wide characterization of d-5’ss that undergo incomplete splicing
WP2. Characterization of regulatory mechanisms at specific d-5’ss

3. Bibliografske reference, ki izhajajo neposredno iz izvajanja projekta

Bo dopolnjeno tekom projekta/to be added