miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs

Abstract

Gemin3 is a DEAD-box RNA helicase that binds to the Survival of Motor Neurons (SMN) protein and is a component of the SMN complex, which also comprises SMN, Gemin2, Gemin4, Gemin5, and Gemin6. Reduction in SMN protein results in Spinal muscular atrophy (SMA), a common neurodegenerative disease. The SMN complex has critical functions in the assembly/restructuring of diverse ribonucleoprotein (RNP) complexes. Here we report that Gemin3 and Gemin4 are also in a separate complex that contains eIF2C2, a member of the Argonaute protein family. This novel complex is a large approximately 15S RNP that contains numerous microRNAs (miRNAs). We describe 40 miRNAs, a few of which are identical to recently described human miRNAs, a class of small endogenous RNAs. The genomic sequences predict that miRNAs are likely to be derived from larger precursors that have the capacity to form stem-loop structures.

Principles and effects of microRNA-mediated post-transcriptional gene regulation

“…RISC was first defined as a large RNA-protein complex with sequence-specific RNA cleavage activity that could be purified by chromatographic fractionation from cells programmed in vivo or in vitro with longer dsRNA or small interfering RNA (siRNA) (Hammond et al, 2000;Zamore et al, 2000). Biochemical approaches and genetic screens in protists, plants, fungi and Caenorhabditis elegans have unambiguously identified the members of the Argonaute protein family as essential protein components of both the cleavage-competent RISCs and the miRNAcontaining ribonucleoproteins (Hammond et al, 2001;Mourelatos et al, 2002;Liu et al, 2004;Meister et al, 2004;Baumberger and Baulcombe, 2005;Qi et al, 2005). Argonaute orthologues have been identified in bacteria, archea and most but not all eucaryotes (Cerutti and Casas-Mollano, 2006).…”

“…The functions of these co-purified factors are largely unknown yet. In human cells Gemin 3 and 4 have been identified in complex together with hAgo2 (Mourelatos et al, 2002;Meister et al, 2005). Both hAgo1 and hAgo2 co-purify with the helicase Mov10, the fly orthologue of which is required for RISC assembly, Tncr6 Bisoform1 and Prmt5 proteins with unknown function (Tomari et al, 2004a;Meister et al, 2005).…”

Principles of micro-RNA production and maturation

“…Mature miRNAs are eventually transferred to Argonaute proteins and serve as guides in RNA silencing (Caudy et al, 2002;Hutva´gner and Zamore, 2002;Ishizuka et al, 2002;Mourelatos et al, 2002;Liu et al, 2004;Meister et al, 2004). In addition to being the effecters of RNA silencing, Argonaute proteins may also contribute to miRNA biogenesis by selecting or binding to and subsequently stabilizing mature miRNAs.…”

Molecular evolution of the rice miR395 gene family

“…These short, single-stranded RNAs are incorporated into the RNA-induced silencing complex (RISC, [11]) and used as a guide to direct posttranscriptional regulation either by cleaving the target mRNA when identical to the pairing site or by repressing protein translation when the miRNA has mismatches with the target sequences [4]. Due to their relative small sizes, many known miRNAs genes in animal genomes form clusters that can be transcribed as a single polycistronic transcript [3,10,12,13]. Co-transcription of functionally different miRNAs provides the opportunity to target several categories of genes simultaneously.…”