Abstract
Regulating the expression of individual miRNAs (microRNAs) is important for cell development and function. The up- or down-regulation of the processing of specific miRNA precursors to the mature active form represents one tool to control miRNA concentration and is mediated by proteins that recognize the terminal loop of the RNA precursors. Terminal loop recognition is achieved by the combined action of several RNA-binding domains. The proteins can then regulate the processing by recruiting RNA enzymes, changing the RNA structure and preventing or enhancing the accessibility and processing activity of the core processing complexes. The present review focuses on how terminal loop-binding proteins recognize their RNA targets and mediate their regulatory function(s), and highlights how terminal loop-mediated regulation relates to the broader regulation of mRNA metabolism.
Highlights
MiRNAs represent a large class of noncoding small RNAs, of ∼22 nt in length, predicted to regulate the expression of more than half of the genes encoded in the human genome [1]
The TL has been shown to be important for the processing of specific miRNAs or groups of miRNAs and, in some cases, a regulatory mechanism that involves trans-acting protein factors binding to the TL has been identified [21,22]
TL-mediated regulation of miRNA biogenesis regulates processes ranging from cellular proliferation to inflammation and muscle and neuronal development
Summary
MiRNAs (microRNAs) represent a large class of noncoding small RNAs, of ∼22 nt in length, predicted to regulate the expression of more than half of the genes encoded in the human genome [1] They control important developmental processes [2], and deregulation of miRNAs has been implicated in various diseases, including different forms of cancer [3,4]. Another RNase III enzyme named Dicer, in association with TRBP (Tar RNA-binding protein) and PACT [protein activator of PKR (double-stranded-RNA-dependent protein kinase)], recognizes the pre-miRNA hairpin structure and cleaves it to a double-stranded miRNA duplex This duplex comprises the mature miRNA ‘guidance strand’, which is loaded in the miRISC (miRNA-induced silencing complex), and the quasi-complementary ‘passenger strand’ that is normally degraded [10,11].
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