Other microRNA-122-responsive messenger RNAs (miR-122-responsive mRNAs)

Other microRNA-122-responsive messenger RNAs (mRNAs) refer to the collective group of endogenous transcripts regulated by miR-122, a highly abundant, liver-specific microRNA (Jopling et al., 2005, Science). Under normal physiological conditions, miR-122 maintains hepatic homeostasis by binding to the 3' untranslated regions of these mRNAs, leading to their degradation or translational repression (Esau et al., 2006, Cell Metabolism). These responsive mRNAs are involved in critical pathways such as cholesterol biosynthesis, iron metabolism, and cell cycle regulation (Roberts et al., 2011, Nucleic Acids Research). In the context of Hepatitis C Virus (HCV) infection, miR-122 is uniquely required for viral replication by binding to the 5' UTR of the viral genome (Jopling et al., 2005, Science). Therapeutic agents like Miravirsen (SPC3649) and RG-101 are designed to sequester miR-122, which effectively inhibits HCV replication (Lanford et al., 2010, Science; Janssen et al., 2013, NEJM). A secondary effect of this sequestration is the 'de-repression' of host miR-122-responsive mRNAs, resulting in increased expression of their encoded proteins. This mechanism explains the observed reduction in serum cholesterol levels in patients treated with miR-122 inhibitors (Janssen et al., 2013, NEJM). However, the broad modulation of these mRNAs poses potential safety concerns, including long-term metabolic changes or the risk of promoting oncogenic pathways (Thibault et al., 2013, Nature Communications). Consequently, these mRNAs are studied as pharmacodynamic markers to assess the systemic impact of miR-122-targeted therapies.

Other names

miR-122 target genesmiR-122 regulated transcriptsmicroRNA-122-responsive mRNAs

Indirect modulation via sequestration of microRNA-122, leading to the de-repression and increased translation of target messenger RNAs.