MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

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

MicroRNAs: Target Recognition and Regulatory Functions

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

MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.

/pdf/micrornas-small-rnas-with-a-big-role-in-gene-regulation-3a05xihg95.pdf

MicroRNAs: small RNAs with a big role in gene regulation

http://bartellab.wi.mit.edu/publication_reprints/Lewis_Cell03.pdf

Prediction of Mammalian MicroRNA Targets

With the discovery of RNA interference (RNAi) and related phenomena, new regulatory roles attributed to RNA continue to emerge. Here we show, in mammalian tissue culture, that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3′ UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs). The mechanism for this repression is cooperative, distinct from the catalytic mechanism of mRNA cleavage by siRNAs. The use of siRNAs to study translational repression holds promise for dissecting the sequence and structural determinants and general mechanism of gene repression by miRNAs.

/pdf/sirnas-can-function-as-mirnas-2get3c1ekg.pdf

siRNAs can function as miRNAs

Short RNAs Repress Translation after Initiation in Mammalian Cells

During RNA interference (RNAi), long dsRNA is processed to ;21 nt duplexes, short interfering RNAs (siRNAs), which silence genes through a mRNA degradation pathway. Small temporal RNAs (stRNAs) and micro-RNAs (miRNAs) are ;21 nt RNAs that are processed from endogenously encoded hairpin-structured precursors, and function to silence genes via translational repression. Here we report that synthetic hairpin RNAs that mimic siRNAs and miRNA precursor molecules can target a gene for silencing, and the mechanism of silencing appears to be through mRNA degradation and not translational repression. The sequence and structural configuration of these RNAs are important, and even slight modification in structure can affect the silencing activity of the hairpins. Furthermore, these RNAs are active when expressed by DNA vectors containing polymerase III promoters, opening the possibility for new approaches in stable RNAi-based loss of function studies.

/pdf/gene-silencing-using-micro-rna-designed-hairpins-518u7efqr7.pdf

Gene silencing using micro-RNA designed hairpins.

How animals establish and pattern the primary body axis is one of the most fundamental problems in biology. Data from diverse deuterostomes (frog, fish, mouse, and amphioxus) and from planarians (protostomes) suggest that Wnt signaling through β-catenin controls posterior identity during body plan formation in most bilaterally symmetric animals. Wnt signaling also influences primary axis polarity of pre-bilaterian animals, indicating that an axial patterning role for Wnt signaling predates the evolution of bilaterally symmetric animals. The use of posterior Wnt signaling and anterior Wnt inhibition might be a unifying principle of body plan development in most animals.

Christian P. Petersen

Papers

siRNAs can function as miRNAs

Short RNAs Repress Translation after Initiation in Mammalian Cells

Gene silencing using micro-RNA designed hairpins.

Wnt Signaling and the Polarity of the Primary Body Axis

Wnt signaling and the polarity of the primary body axis.