Regulación post-transcripcional del clúster MIR-23-MIR-27-MIR-24 mediada por el factor de transcripción MEF2C
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2016
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Jaén: Universidad de Jaén
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[ES]El factor de transcripción MEF2C es capaz de regular transcripcionalmente a nivel cardiaco. Por otro lado, los microRNAs son una familia de ARNs no codificantes de ~ 22 nucleótidos (nt) de tamaño. Hasta hace poco, se pensaba que MEF2C solo podía regular a los microRNAs a nivel transcripcional, pero estudios recientes han demostrado que quizás puedan existir mecanismos de regulación post-transcripcional de MEF2C sobre microRNAs, en concreto sobre el clúster de microRNAs miR-23a-miR-27a-miR-24-2. Para comprobar si existe dicha regulación post-transcripcional, se llevará a cabo el diseño de dos construcciones de MEF2C, una con delección en el extremo 3´ y la otra con delección en el extremo 5´, para ver la contribución reguladora de cada parte a nivel post-transcripcional (pre-miRNAs y microRNAs maduros) sobre dicho clúster. Los resultados obtenidos muestran que el extremo 3´ regula a nivel de microRNAs maduros, estimulando la expresión del miR-23a e inhibiendo la expresión de miR-27a y miR-24-2, regulación que podría ser llevada a cabo por un dominio, aún no muy estudiado, en el extremo 3´ de MEF2C. Por otro lado, el extremo 5´ regula a nivel de microRNAs maduros, estimulando la expresión del miR-23a; y regula también a nivel de pre-miRNAs, estimulando la expresión de los premiRs-23a y-24-2. Dicha regulación en el extremo 5´ podría ser llevada a cabo por los dos dominios presentes en el extremo 5´ de MEF2C, que son MADS-MEF2-LIKE y HJURP_C.
[EN]The transcription factor MEF2C is able to regulate transcriptionally at the cardiac level. Moreover, microRNAs are a family of non-coding RNAs of ~ 22 nucleotides (nt) in size. Until recently, it was thought that MEF2C could only regulate the microRNAs at the transcriptional level, but recent studies have shown that perhaps there may exist mechanisms of post-transcriptional regulation of MEF2C on microRNAs, in particular on the cluster of microRNAs miR-23a-miR-27a-miR-24-2. To check if the post-transcriptional regulation exists, it will be held the design of two MEF2C constructions, one with deletion at the 3' end, and the other with deletion at the 5' end, to see the regulatory contribution of each part to post-transcriptional level (pre-miRNAs and mature microRNAs) on that cluster. The results show that the 3' end regulates at mature microRNAs level, stimulating the expression of miR-23a and inhibiting the expression of miR-27a and miR-24-2, regulation that could be carried out by a domain, not yet studied, at the 3' end of MEF2C. On the other hand, the 5' end regulates at the mature microRNAs level, stimulating the expression of miR-23a; and it also regulates at the pre-miRNAs level, stimulating the expression of premiRs-23a and-24-2. Such regulation at the 5' end could be carried out by the two domains present at the 5' end of MEF2C, which are MADS-MEF2-like and HJURP_C.
[EN]The transcription factor MEF2C is able to regulate transcriptionally at the cardiac level. Moreover, microRNAs are a family of non-coding RNAs of ~ 22 nucleotides (nt) in size. Until recently, it was thought that MEF2C could only regulate the microRNAs at the transcriptional level, but recent studies have shown that perhaps there may exist mechanisms of post-transcriptional regulation of MEF2C on microRNAs, in particular on the cluster of microRNAs miR-23a-miR-27a-miR-24-2. To check if the post-transcriptional regulation exists, it will be held the design of two MEF2C constructions, one with deletion at the 3' end, and the other with deletion at the 5' end, to see the regulatory contribution of each part to post-transcriptional level (pre-miRNAs and mature microRNAs) on that cluster. The results show that the 3' end regulates at mature microRNAs level, stimulating the expression of miR-23a and inhibiting the expression of miR-27a and miR-24-2, regulation that could be carried out by a domain, not yet studied, at the 3' end of MEF2C. On the other hand, the 5' end regulates at the mature microRNAs level, stimulating the expression of miR-23a; and it also regulates at the pre-miRNAs level, stimulating the expression of premiRs-23a and-24-2. Such regulation at the 5' end could be carried out by the two domains present at the 5' end of MEF2C, which are MADS-MEF2-like and HJURP_C.