DOES THE MIRNA PATHWAY HAVE KRABS? UNDERSTANDING THE NOVEL ROLE OF KRBOX4 IN THE MIRNA PATHWAY
Post-transcriptional regulation is a major component of gene regulation and is particularly important in mammals and other complex animals. Small non-coding RNAs, known as microRNAs (miRNAs), regulate a wide range of genes post-transcriptionally. By interacting with targets within the 3′ untranslated region (UTR), miRNAs destabilize mRNAs, thereby repressing protein production and translation. The miRNA pathway (which includes miRNA biogenesis) entails a series of processing steps which are crucial to the control of miRNA abundance within cells. Dysregulation of individual miRNAs is often consequential as miRNAs are involved in many biological processes including development, immune function and more. Therefore, understanding the miRNA pathway is paramount. There is much that is still poorly understood regarding the biogenesis of individual miRNAs. Therefore, I sought to identify new components required for miRNA function to facilitate improved understanding of the pathway. A reverse genetic screen identified a number of potential novel miRNA pathway components. One of the identified genes encodes a putative zinc finger transcription factor, known as KRBOX4. KRBOX4 is unique structurally in comparison to other members of the same protein family, which has generated questions as to how it functions within the miRNA pathway. Changes in KRBOX4 expression consequentially leads to proportional changes in let-7 expression and activity. The current model suggests that KRBOX4 promotes let-7 maturation through inhibition of Lin28. Furthermore, KRBOX4’s regulatory role also extends beyond let-7. Characterization of novel factors and further study of KRBOX4 promises to facilitate an even greater understanding of miRNAs and their role in post-transcriptional gene regulation.