MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

http://bartellab.wi.mit.edu/publication_reprints/Bartel_Cell09.pdf

MicroRNAs: Target Recognition and Regulatory Functions

Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.

The functions of animal microRNAs

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

/pdf/microrna-expression-profiles-classify-human-cancers-43jqfv3rwu.pdf

MicroRNA expression profiles classify human cancers

Evidence that a "four-cell cluster" may prime cytotoxic T-cells during graft rejection.

defects opposite to those of lin-4(e912). Precisely the These opposite developmental timing defects of lin-4 Harvard Medical School and lin-14 mutants, and the fact that loss of lin-14 is Department of Molecular Biology epistatic to lin-4(e912), suggested that the lin-4(e912) Massachusetts General Hospital mutation resulted in an excess of lin-14 activity. So lin-4 Boston, Massachusetts 02114 might encode a transacting negative regulator of lin-14. This view was reinforced by another oddly lucky event: while screening worm populations for an entirely different class of mutant, Victor was startled to find an The intellectual backdrop motivating our effort to clone animal that looked exactly like the very distinctive lin-lin-4 (Lee et al., 1993) had nothing to do with questions 4(e912) animals! This fortuitous new mutation, n355, was about noncoding RNAs or antisense gene regulation. a dominant allele of lin-14. Constitutive activity of lin-We were simply curious about an interesting worm mu-14 resulted in the same collection of retarded develop-tant, and everything we found out about it was unex-mental timing defects as loss of lin-4. A quick look pected. We consider ourselves very lucky to happen to through the Horvitz lab collection of egg-laying mutants have chosen lin-4 to study. In fact, good fortune ap-isolated by Nancy Tsung revealed a second lin-14 gain-peared at many steps before and during our lin-4 project, of-function allele, n536. often through the contributions of other people. Victor worked with Gary Ruvkun to clone lin-14 in the lin-4 was discovered in Sydney Brenner's lab in the Horvitz lab (Ruvkun et al., 1989), and Gary went on to mid 1970s through the isolation of a mutation (e912). sequence the lin-14 (a novel nuclear protein) gene in his The remarkable developmental defects of lin-4(e912) own lab at MGH (Ruvkun and Giusto, 1989). Gary's lab were first described by Horvitz and Sulston (1980) and discovered that the n355 and n536 gain-of-function mu-characterized in detail by Chalfie et al. (1981). lin-4(e912) tations are deletions in the 3Ј untranslated region (UTR) animals look terrible: they grow into long, thin " adults " of the lin-14 mRNA, and that LIN-14 protein level is with a larval skin, and they fail to stop molting at the posttranscriptionally downregulated during worm de-normal stage and thus undergo extra larval stages. Chal-velopment (Wightman et al., 1991). Therefore, if lin-4 fie et al. (1981) showed that e912 hermaphrodites and were involved in the temporal regulation of lin-14, it males …

Rosalind C. Lee

Papers

Evidence that a "four-cell cluster" may prime cytotoxic T-cells during graft rejection.

Commentary A Short History of a Short RNA