Why do miRNAs live in the miRNP?

Do tiny RNAs now have a home?

Noncoding RNAs function in diverse pathways—dosage compensation, gene imprinting, transcriptional regulation, pre-mRNA splicing, and the control of mRNA translation—and they carry out these roles from within specific RNA–protein complexes that ensure each noncoding RNA is in the right cellular compartment with the appropriate proteins needed to accomplish its biochemical function. Thus, identifying the ribonucleoprotein complex (RNP) associated with a noncoding RNA gives clues to its cellular function and biochemical mechanism by revealing the proteins whose company it keeps. The discovery by Dreyfuss and coworkers that microRNAs reside in a ∼550-kD (15S) particle provides new clues toward the functions of this novel and surprisingly large class of tiny, noncoding RNAs (Mourelatos et al. 2002).

The first microRNA, (miRNA) lin-4, was identified in 1993 (Lee et al. 1993). Ambros and coworkers positionally cloned thelin-4 gene, a locus required for the correct timing of development in Caenorhabditis elegans, only to find that the gene encodes no protein (Lee et al. 1993). Instead,lin-4 comprises two small noncoding RNAs, one 22 nucleotides long, and a longer form, lin-4L, that can fold into a hairpin structure. Seven years later, Ruvkun and colleagues discovered thatlet-7, which likewise regulates developmental timing in worms, is also a tiny, noncoding RNA (Reinhart et al. 2000). Becauselin-4 and let-7 control developmental timing, they have been dubbed small temporal RNAs (stRNAs). Recently, three laboratories succeeded in cloning additional stRNA-like RNAs from worms, flies, and human cells (Lagos-Quintana et al. 2001; Lau et al. 2001; Lee and Ambros 2001). These efforts uncovered a wealth of 19–25 nucleotide RNAs, including lin-4 and let-7, which are collectively known as miRNAs (for reviews, see Moss 2001; Ruvkun 2001;Banerjee and Slack 2002). These efforts added an additional 100 tiny RNAs to the …