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.

(https://www.micropublication.org/media/2020/01/Screen-Shot-2020-01-11-at-5.29.58-PM.png) Figure 1: A. Example side-by-side micrograph of FLAG::degron::ERFA-3 and degron::ERFA-3;TIR1 adult animals. Expression tagged with mRuby was visualized by fluorescence microscopy. The shorter and thicker appearance of the TIR1 expressing s characteristic of the dumpy phenotype. B. Western blot of ERFA-3 protein levels in FLAG::degron::ERFA-3 and FLAG::degron::E TIR1 mixed-stage animals cultured at 15°C. C. Western blot of ALG-1 protein levels in N2 and FLAG::degron::ALG-1; TIR1 L4 animals cultured at 20°C.

https://www.micropublication.org/pdf/micropub-biology-000213

Auxin-independent depletion of degron-tagged proteins by TIR1.

MicroRNAs (miRNAs) are small RNA molecules that posttranscriptionally regulate the expression of protein-coding genes. The mature miRNAs are loaded into Argonaute-containing protein complexes (miRISC, miRNA Induced S  ilencing Complex), and guide these complexes to the 3' UTR of targeted mRNA transcripts via base-pairing interactions. However, the imperfect complementarity that characterizes the interactions between animal miRNAs and target sites complicates the identification of direct target genes. We developed a biochemical method to identify on a large scale the target sequences recognized by miRISC in vivo. The mRNA sites bound by miRISC are stabilized by cross-linking and isolated by immunoprecipitation of Argonaute-containing complexes. The bound RNA molecules are trimmed to the regions protected by Argonaute, subjected to a series of isolation and linker ligation steps and identified by high-throughput sequencing methods.

Comprehensive identification of miRNA target sites in live animals.

This research aims to extend the existing knowledge on air quality improvement by the arboreal–shrub heritage. The PM accumulation (PM10–100, PM2.5–10, and PM0.2–2.5 (µg·cm−2)) was measured with consolidated gravimetric techniques during spring, summer, and fall for 2160 leaf samples belonging to the basal, median, and apical part of the crown of 17 species located in the streets and parks of 2 European cities (Rimini and Krakow). On the same samples, the deposition (PM10 and PM2.5 (µg·cm−2·day−1)) was evaluated according to a model based on the wash-off rain effect. Quercus ilex accumulated more PMx than the other species in Rimini, while in Krakow, the highest accumulators were Pinus nigra for PM10–100, Tilia cordata for PM2.5–10, and Populus nigra for PM0.2–2.5. Only in Krakow was the capture capacity of some species affected by the street or park growing condition. The basal leaves showed greater PM10–100 accumulation than the median and apical ones. In Rimini, the total PM accumulation tended to increase throughout the year, while in Krakow, the opposite occurred. However, as the accumulation increased, the deposition decreased. The PM accumulation was reduced by rainfall and enhanced by the air PM concentration, while the wind speed effect was opposite, depending on the city. These findings are useful for directing decision makers in the design of greener, healthier, and sustainable cities.

/pdf/particulate-pollution-capture-by-seventeen-woody-species-1wlijhrw.pdf

Particulate Pollution Capture by Seventeen Woody Species Growing in Parks or along Roads in Two European Cities

The heat shock response (HSR) is a highly conserved cellular process that promotes survival during stress. A hallmark of the HSR is the rapid induction of heat shock proteins (HSPs), such as HSP-70, by transcriptional activation. Once the stress is alleviated, HSPs return to near basal levels through incompletely understood mechanisms. Here, we show that the microRNA pathway acts during heat shock recovery in Caenorhabditis elegans. Depletion of the miRNA Argonaute, Argonaute Like Gene 1 (ALG-1), after an episode of heat shock resulted in decreased survival and perdurance of high hsp-70 levels. We present evidence that regulation of hsp-70 is dependent on miR-85 and sequences in the hsp-70 3'UTR that contain target sites for this miRNA. Regulation of hsp-70 by the miRNA pathway was found to be particularly important during recovery from HS, as animals that lacked miR-85 or its target sites in the hsp-70 3'UTR overexpressed HSP-70 and exhibited reduced viability. In summary, our findings show that down-regulation of hsp-70 by miR-85 after HS promotes survival, highlighting a previously unappreciated role for the miRNA pathway during recovery from stress.

/pdf/recovery-from-heat-shock-requires-the-microrna-pathway-in-3tsz4ep65i.pdf

Recovery from heat shock requires the microRNA pathway in Caenorhabditis elegans.

The let-7 miRNA (microRNA) is an essential regulator of development from nematode worms to humans. Altered expression of let-7 results in larval arrest or lethality in Caenorhabditis elegans. Likewise, under- or over-expression of let-7 in human cells can result in cellular overproliferation or halted cell division respectively. Thus the biogenesis of this critical miRNA is controlled at multiple levels. An unexpected mechanism for regulating the initial processing of let-7 was recently found to involve the let-7 miRNA itself. The mature let-7 miRNA along with its effector protein, Argonaute, were shown to bind to a site in the primary transcripts produced by the let-7 gene. This interaction enhances processing through a novel auto-regulatory feedback loop. This discovery highlights a new role for the miRNA complex in regulating miRNA biogenesis and enriches the classes of RNAs targeted by Argonaute.

Abbreviations: ALG-1, Argonaute-like gene 1; CLIP, cross-linking and immunoprecipitation; DGCR8, DiGeorge syndrome critical region gene 8; HBL-1, hunchback-like 1; hnRNPA1, heteronuclear ribonucleoprotein A1; miRNA, microRNA; miRISC, miRNA-induced silencing complex; pri-let-7, primary let-7; RBP, RNA-binding protein; XPO5, exportin 5

Amy E. Pasquinelli

Papers

Auxin-independent depletion of degron-tagged proteins by TIR1.

Comprehensive identification of miRNA target sites in live animals.

Particulate Pollution Capture by Seventeen Woody Species Growing in Parks or along Roads in Two European Cities

Recovery from heat shock requires the microRNA pathway in Caenorhabditis elegans.

The primary target of let-7 microRNA