ComPreValRther · Computational Prediction and Validation of RNA thermometer at transcriptome-wide scale in living cell

Computational Prediction and Validation of RNA thermometer at transcriptome-wide scale in living cell

All life forms on earth are affected by temperature. Temperature is crucial to plant growth and development. Cold and heat stresses may drastically inhibit plant growth and cause yield losses in crops. Previous studies have focused on temperature-regulated transcriptional network; however, the transcriptional regulation of mRNA levels only partially correlates with translation. It is therefore important to elucidate the mechanisms underpinning post-transcription regulation of gene expression. RNA molecules fold into secondary and tertiary structures, which can play key roles in transcription, splicing, translation, localization and degradation. Recently, studies on RNA structures have drawn much attention. So far RNA thermometers (RNATs) have mostly been identified in bacteria. RNATs respond to temperature shifts by changing their secondary structure. RNATs usually fold into a complex structure typically positioned in the 5’ UTR of mRNAs, to modulate translation by affecting ribosomal association in response to temperature shifts. Traditional RNA structure probing experiments are mainly based on in vitro treatment of a synthesised RNA sequence with various chemical or enzymatic probes to distinguish single and paired nucleotides. Thus, most RNATs in bacteria have been identified via in silico or in vitro conditions. However, the in silico / in vitro structure of RNA species will be different from those characterised in vivo as a living cell is usually out of equilibrium and the actual structure of RNA species will be heavily dependent on temperature, interacting proteins and nucleotides. In vivo RNA structure determination has always been a challenging but active interdisciplinary research field involving nucleic acids chemistry, biophysics, biochemistry and molecular biology. I took advantage of this novel method in vivo RNA structure profiling developed in the Ding lab to fundamentally understand the functional role of RNA structure in translation and how RNA structure alters in response to temperature in living cells. My project aimed to develop pipelines to quantitatively measure in vivo RNA structure features and identify their changes in response to temperature through modelling and data mining.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз