MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Tales of Detailed Poly(A) Tails

MicroRNAs: deviants no longer.

SUMMARY The22nucleotidelet-7smalltemporalRNAhasbeen found consistently in samples from diverse bilateria butnot from sponge or cnidarians. Here we further examine thephylogenetic distribution of this regulatory RNA by samplingrepresentativesofdiversemetazoan lineages.The22nucleo-tide let-7 RNAisdetectableintricladandpolycladplatyhelminths,nemertean, and chaetognath but not ctenophore or acoelmetazoans. These results support recent arguments thatacoels are distinct from other acoelomate platyhelminths. Weargue that let-7 is not a bilaterian or triploblast synapomorphybut instead evolved later in metazoan evolution, perhaps inassociation with complex life history traits. INTRODUCTION The let-7 gene was ﬁrst identiﬁed in the nematode Caeno-rhabditis elegans as an essential regulator of developmentaltiming (Reinhart et al. 2000). It encodes a 22 nucleotide (nt)RNA that negatively regulates the expression of protein-coding genes that contain regions of complementarity in their3 0 -untranslated regions (UTRs) (Reinhart et al. 2000; Slacket al. 2000). Expression of let-7 RNA is undetectable until thelast larval stages in C. elegans, where it directs larval to adultcell fate transitions in certain tissues (Reinhart et al. 2000). Amajor target of let-7 mediated down-regulation is the lin-41protein-coding gene, which contains two complementary sitesin its 3

Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution?

Originally discovered in C. elegans, microRNAs (miRNAs) are small RNAs that regulate fundamental cellular processes in diverse organisms. MiRNAs are encoded within the genome and are initially transcribed as primary transcripts that can be several kilobases in length. Primary transcripts are successively cleaved by two RNase III enzymes, Drosha in the nucleus and Dicer in the cytoplasm, to produce ∼70 nucleotide (nt) long precursor miRNAs and 22 nt long mature miRNAs, respectively. Mature miRNAs regulate gene expression post-transcriptionally by imperfectly binding target mRNAs in association with the multiprotein RNA induced silencing complex (RISC). The conserved sequence, expression pattern, and function of some miRNAs across distinct species as well as the importance of specific miRNAs in many biological pathways have led to an explosion in the study of miRNA biogenesis, miRNA target identification, and miRNA target regulation. Many advances in our understanding of miRNA biology have come from studies in the powerful model organism C. elegans. This chapter reviews the current methods used in C. elegans to study miRNA biogenesis, small RNA populations, miRNA-protein complexes, and miRNA target regulation.

/pdf/analysis-of-microrna-expression-and-function-xczs3f9gxc.pdf

Analysis of microRNA expression and function.

We have cloned the chicken and mouse orthologues of the Caenorhabditis elegans heterochronic gene lin-41. During limb development, lin-41 is expressed in three phases over developmental time and most notably is associated with the developing autopod. Using chicken and mouse mutants and bead implantations, we report that lin-41 is genetically and biochemically downstream of both the Shh and Fgf signaling pathways. In C. elegans, it is proposed that lin-41 activity is temporally regulated by miRNAs (let-7 and lin-4) that bind to complementary sites in the lin-41 3′-untranslated region (UTR). Taking a bioinformatics approach, we also report the presence of potential miRNA binding sites in the 3′-UTR of chicken lin-41, including sites for the chicken orthologues of both C. elegans let-7 and lin-4. Finally, we show that these miRNAs and others are expressed in the chick limb consistent with the hypothesis that they regulate chicken Lin-41 activity in vivo. Developmental Dynamics 234:948–960, 2005. © 2005 Wiley-Liss, Inc.

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.20591

Amy E. Pasquinelli

Papers

Tales of Detailed Poly(A) Tails

MicroRNAs: deviants no longer.

Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution?

Analysis of microRNA expression and function.

Analysis of the regulation of lin-41 during chick and mouse limb development