Mirtrons: microRNA biogenesis via splicing

Abstract

A well-defined mechanism governs the maturation of most microRNAs (miRNAs) in animals, via stepwise cleavage of precursor hairpin transcripts by the Drosha and Dicer RNase III enzymes. Recently, several alternative miRNA biogenesis pathways were elucidated, the most prominent of which substitutes Drosha cleavage with splicing. Such short hairpin introns are known as mirtrons, and their study has uncovered related pathways that combine splicing with other ribonucleolytic machinery to yield Dicer substrates for miRNA biogenesis. In this review, we consider the mechanisms of splicing-mediated miRNA biogenesis, computational strategies for mirtron discovery, and the evolutionary implications of the existence of multiple miRNA biogenesis pathways. Altogether, the features of mirtron pathways illustrate unexpected flexibility in combining RNA processing pathways, and highlight how multiple functions can be encoded by individual transcripts.

Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression?

“…Recent studies have pointed out alternative pathways for maturation of certain miRNAs that deviate from the canonical miRNA biogenesis pathway bypassing one of the RNase III cleavage steps [72][73][74]. This is the case of the mirtrons, pre-miRNA hairpins generated by splicing and debranching of short hairpin introns, and other small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs), tailed endogenous shRNA, long hairpin RNAs (hp-RNAs) derived from short interspersed nuclear elements (SINEs) that bypass the cleavage step of Drosha [75][76][77]. To date, miR-451, an erythropoietic miRNA conserved in vertebrates, is instead the only Dicer-independent miRNA identified [78].…”

Efectos de los RNAm maternos sobre la maduración del ovocito y el desarrollo embrionario temprano en mamíferos

“…The miRNAs are encoded within the intragenic regions (49) and within intronic regions (50) . Those encoded in intragenic regions are expressed under the action of RNApol II and referred to as pri-miRNAs (primary miRNA); these are processed by a complex of ribonucleic protein, the enzyme DROSHA and protein DGCR8 that cut to the pri-miRNA and leave it in structure of stem-bubble (51,52) .…”

“…Los miRNAs están codificados dentro de regiones intergénicas (49) y dentro de regiones intrónicas (50) . Los que están codificados en regiones intergénicas se expresan bajo la acción de la RNApol II y se denominan pri-miRNAs (miRNA primario), estos son procesados por un complejo ribonucleico proteico, compuesto por la enzima DROSHA y la proteína DGCR8 que cortan al pri-miRNA y lo dejan en estructura de tallo burbuja (51,52) .…”

“…Sea cual sea la vía de procesamiento del tallo-burbuja, el resultado es el mismo, un precursor de miRNA (pre-miRNA) con estructura tallo-burbuja, el cual pasa al citoplasma a través de la proteína EXPORTINA5, donde es cortado por DICER, una RNasa III, para obtener 2 miRNAs de aproximadamente 20 pb. Una de las cadenas se selecciona para funcionar como un miRNA maduro, mientras que la otra cadena es degradada (50,53,54) . En ocasiones, las dos hebras de la horquilla del pre-miRNA dan lugar a dos miRNAs maduros (51) .…”

“…Whatever the way of processing of the stem-bubble, the result is the same, a precursor miRNA (pre-miRNA) with stem-bubble structure, which goes to the cytoplasm through the protein EXPORTIN5, which is cut by DICER, an RNase III, to get 2 miRNAs of approximately 20 pb. One of the chains is selected to run as a mature miRNA, while the other chain is degraded (50,53,54) . Occasionally, the two strands of the fork of the pre-miRNA give rise to two mature miRNAs (51) .…”