LOX MRNA SILENCING · Mechanism of translational silencing of lipoxygenase mRNA
6РП — Действия „Мария Кюри“
- Период
- 2004-07-01 → 2006-06-30
- Финансиране от ЕС
- 149 722 €
- Участници
- 1
- Схема
- IIF
Линиите свързват координатора с партньорите.
Накратко на български
Механизмът, по който протеини блокират синтеза на липоксигеназа в еритроцитите, се анализира чрез специфични елементи в тяхната мРНК. Разбирането на този процес помага да се разбере как клетките контролират експресията на своите гени.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Цел на проекта
Background: In differentiating cells, translation of many mRNAs encoding late-acting proteins issilenced until these proteins are needed. During terminal differentiation of erythrocytes, 15-Lipoxygenase (LOX) protein expression is regulated by a specific s equence element ('DICE') in the 3'untranslated region (UTR) of its mRNA. Previous work from the Hentze lab has shown that the RNAbinding proteins hnRNP K and E1 bind to the DICE in vivo and in vitro, inhibiting translation at the 60Sribosomal subunit joini ng step by an unknown mechanism.Objective: Our objective is to determine the precise molecular mechanism of action of the LOX/DICE3'UTR silencing complex by identifying the functional and physical links that connect the complex tothe initiating ribosome. W e will test two major hypotheses: (1) silencing requires specific molecularinteractions between hnRNPK/E1 and an initiation factor mediating subunit joining or (2) it requiresinteraction with a specific ribosomal structure, and this interaction inhibits su bunit joining.Approach: To identify functional targets of the DICE complex, a reconstituted in vitro translation initiationassay will be adapted to study DICE-mediated silencing. With this system, we will test the hypothesisthat the DICE complex inhibits s ubunit joining by modulating the activity and/or association of specifictranslation initiation factors. To identify specific molecular contacts made by and required for DICE-mediated silencing we will use two complementary approaches: (1) structure-guided site-specificmutagenesis approaches, followed by analysis in established cell culture and in vitro assays; (2) affinity-directed mass spectrometry ('functional proteomics') to directly identify interactions.Medical Relevance: Inappropriate control of gene expression in general, and of tumor suppressorgenes and oncogenes in particular, is a major component in molecular etiology of cancer. Aberrant#'
Оригинален текст от CORDIS (на английски).
Участници
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HEIDELBERGКоординаторГермания
Връзки
Данни: CORDIS, © Европейски съюз