Article

How to control miRNA maturation?

Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, La Jolla, CA, USA.
RNA biology (Impact Factor: 5.56). 11/2009; 6(5):536-40.
Source: PubMed

ABSTRACT In this point of view we discuss the role of co-activators and co-repressors of miRNA precursors maturation, the possibility that their functions are post translationally regulated by different signaling pathways, and their potential role in the miRNA-dependent control of cell proliferation and differentiation.

1 Bookmark
 · 
216 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA duplices are separated into a guide and a passenger strand. By convention, the guide represents the active microRNA while the passenger is supposedly degraded. However, passenger strands also emerge as active microRNAs. It is unknown whether the guide-to-passenger-strand ratio can be actively regulated and which factors influence strand incorporation into the RISC. Here, we identify a microRNA with a variable guide-to-passenger-strand ratio along with its regulatory factor: Human Argonaute-3 specifically enhances the passenger strand expression and activity of the tumor suppressor microRNA let-7a. This post-maturational effect is mediated by the Ago3 PAZ and MID domains yielding an elevated affinity for let-7a-3p. Notably, this is independent of the 5'-terminal basepair stability, challenging the universality of the respective rule for microRNA strand selection. Thus, this study uncovers the first protein regulator of the ratio between microRNA guide and passenger strand expression and activity.
    RNA biology 10/2013; 10(10). · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Biochemical Society Transactions 08/2013; 41(4):861-5. · 2.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional mechanisms: i) by promoting decay of unstable mRNAs and ii) by favoring maturation from precursors of select microRNAs (miRNAs) including the prototypical tumor suppressor let-7. Studies performed in primary and cultured cells as well as in mice proved that the ability of KSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response.
    Seminars in Cell and Developmental Biology 05/2014; · 6.20 Impact Factor