Congratulations to Roza Przanowska who is a second year graduate student and has just been awarded an American Heart Association Fellowship to begin 7/1/18. Her project is entitled “Structure-function studies of IncRNAs involved in myogenesis” and the details are below.
The project summary:
Heart failure (HF) is a huge problem in the modern world, only in the United States ~5.7 million adults have HF and 1 in 9 deaths in 2009 had HF as a contributing cause. HF occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the organism’s needs. There is whole variety of potential causes of HF and the most common ones are: myocardial infarction (e.g. after heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and various cardiomyopathies. However, HF not only destroys heart function, but it also leads to whole body changes. One of them is skeletal muscle wasting and impairment of their metabolism, structure and function. Skeletal muscles have a regeneration potential – the muscle stem cells (satellite cells) offer the possibility of functional recovery or hypertrophy following injury or exercise. Moreover, C2C12 skeletal muscle myoblasts were used to sustain and potentially restore heart function after injury by forming differentiated grafts in mouse ventricular myocardium. There are many factors involved in myogenesis (muscle differentiation): transcription factors (TFs) (pairedhomeobox TFs, basic helix-loop-helix (bHLH) TFs, muscle specific regulatory factors), and non-coding RNAs: miRNA and lncRNA. We performed bioinformatic analysis to identify new lncRNAs involved in myogenesis and focused on two of them: MUNC and MT2953. MUNC (MyoD-Upstream-Non-Coding) lncRNA is specifically expressed in skeletal muscle, upregulated during differentiation and knockdown of MUNC in vivo impaired murine muscle regeneration. Human MUNC is induced during differentiation of myoblasts and knockdown decreases differentiation as well, what suggests an evolutionarily conserved role of MUNC. Therefore, I hypothesize that mouse and human MUNC even though they are not identical in sequence, are similar in structure. MT2953 is newly discovered lncRNA, which is upregulated in heart and skeletal muscles as well. In my research, I will test whether these lncRNAs have specific structural domains important for myogenesis. By determining structure of mouse and human homologs, effects of known SNPs on lncRNA folding (presented in Aim 1) with combination of experimental structure-function data (Aim 2) we will be able understand how structure correlates with functions. Those informations will also be very useful for understanding myocardiac regeneration and other related cardiovascular problems.
Roza is a current Graduate Student in the lab of Dr. Anindya Dutta.