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Preurejanje transkripta serotoninskega receptorja 2C pri miših, izpostavljenih obogatenemu okolju = RNA editing of the serotonin receptor 2C transcript in mice exposed to enriched environment : enovitni magistrski študij farmaciijaHertl, GregorSerotoninski receptor 2c je izjemno pomemben za delovanje centralnega živčnega sistema (CŽS), saj sodeluje pri uravnavanju procesov prehranjevanja, razpoloženja, vedenja, motorike in kognitivnih ... funkcij. Njegovo aktivnost uravnavata dve posttranskripcijski modifikaciji - preurejanje adenozinov (A) v inozine (I) na pre-mRNA in alternativno povezovanje eksonov. Obe močno vplivata na funkcionalnost receptorja. Preurejanje RNA A v I katalizirajo na RNA delujoče adenozin deaminaze (ADAR) na alternativnem eksonu Vb na petih bližnjih mestih adenozinov (A, B, C, D in E), kar lahko povzroči spremembo kodonov in s tem aminokislinskega zaporedja druge znotrajcelične zanke, s katero receptor vstopa v interakcije s proteini G. Posttranskripcijske modifikacije na pre-mRNA 5ht2c (in posledično funkcionalnost receptorja) uravnava mala nukleolarna RNA (snoRNA) SNORD115, ki vsebuje evolucijsko ohranjen segment nukleotidov, ki je komplementaren alternativnemu eksonu Vb. SNORD115 uravnava alternativno povezovanje eksonov z vezavo na utiševalno zaporedje, kar spodbudi vključitev eksona Vb v zrelo mRNA ter nastanek učinkovite dolge izooblike receptorja. Predvidevamo tudi, da SNORD115 z vezavo na ekson Vb blokira preurejanje transkripta 5ht2c in tako poveča signalizacijsko sposobnost receptorja. Izbris dela kromosona, ki nosi zapis za gen SNORD115@, povzroči nastanek Prader-Willijevega sindroma. Na izražanje genov za ADAR in SNORD115 lahko vpliva več dejavnikov: okolje, genetika, zdravljenje z zdravili in izpostavitev stresu v mladosti in odraslosti. V okviru našega magistrskega dela smo preučevali vpliv genetike (sev) in okolja (obogateno in standardno) na izražanje obeh genov v prefrontalnemu korteksu možganov miši BALB/c in C57BL/6, ki se razlikujeta po nivojih serotonina v CŽS, z metodo qPCR. Dodatno smo z metodo sekvenciranja nove generacije (NGS) analizirali izražanje in frekvenco posameznih izooblik mRNA, ter obseg deaminacij adenozinov na posameznih položajih (A-E). Ugotovili smo, da tako genetsko ozadje kot izbira okolja (obogateno ali standardno) vsaj v izbranem časovnem oknu 4 tednov nimata pomembnega vpliva na izražanje obeh genov v prefrontalnemu korteksu možganov miši. Njun vpliv na izražanje posameznih izooblik in mest preurejanja pre-mRNA 5ht2c je zanemarljiv.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [G. Hertl], 2019Language - slovenianCOBISS.SI-ID - 4807793
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Faculty of Pharmacy, Ljubljana | Ljubljana | FFALJ |
reading room 1 cop.
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Hertl, Gregor | ![]() |
Bratkovič, Tomaž, farmacevt, 1978- | 23598 |
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