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

We have mapped and quantified mouse transcriptomes by deeply sequencing them and recording how frequently each gene is represented in the sequence sample (RNA-Seq). This provides a digital measure of the presence and prevalence of transcripts from known and previously unknown genes. We report reference measurements composed of 41–52 million mapped 25-base-pair reads for poly(A)-selected RNA from adult mouse brain, liver and skeletal muscle tissues. We used RNA standards to quantify transcript prevalence and to test the linear range of transcript detection, which spanned five orders of magnitude. Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors. RNA splice events, which are not readily measured by standard gene expression microarray or serial analysis of gene expression methods, were detected directly by mapping splice-crossing sequence reads. We observed 1.45 × 10 5 distinct splices, and alternative splices were prominent, with 3,500 different genes expressing one or more alternate internal splices. The mRNA population specifies a cell’s identity and helps to govern its present and future activities. This has made transcriptome analysis a general phenotyping method, with expression microarrays of many kinds in routine use. Here we explore the possibility that transcriptome analysis, transcript discovery and transcript refinement can be done effectively in large and complex mammalian genomes by ultra-high-throughput sequencing. Expression microarrays are currently the most widely used methodology for transcriptome analysis, although some limitations persist. These include hybridization and cross-hybridization artifacts 1–3 , dye-based detection issues and design constraints that preclude or seriously limit the detection of RNA splice patterns and previously unmapped genes. These issues have made it difficult for standard array designs to provide full sequence comprehensiveness (coverage of all possible genes, including unknown ones, in large genomes) or transcriptome comprehensiveness (reliable detection of all RNAs of all prevalence classes, including the least abundant ones that are physiologically relevant). Other

/pdf/mapping-and-quantifying-mammalian-transcriptomes-by-rna-seq-1egh5oivst.pdf

Mapping and quantifying mammalian transcriptomes by RNA-Seq.

https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The efficacy of a newly created software package for predictive modeling of developmental gene regulatory networks (GRNs) has recently been demonstrated (Peter et al., 2012). The program GeNeTool computes spatial gene expression patterns based on GRN interactions and thereby allows the direct comparison of predicted and observed spatial expression patterns. GeNeTool also permits in silico exploration of both cis- and trans- perturbations of GRN interactions. Here, we present this program, review briefly its major features and applications, and provide a detailed and accessible tutorial.

https://hal.inria.fr/hal-01101032/document

A new software package for predictive gene regulatory network modeling and redesign.

I – From Genome to Embryo: The Regulation of Gene Activity in Early Development

This chapter provides an overview of the genomic control apparatus and its causal role in development and evolution. The regulatory interactions mandated by the gene control circuitry determine whether each gene is expressed in every cell, throughout developmental space and time and if so, at what amplitude. In physical terms the control circuitry encoded in the deoxyribonucleic acid (DNA) is comprised of cis-regulatory elements. cis-regulatory elements are information processing units “wired” into the regulatory network so that they receive multiple inputs, in the form of the multiple transcription factors that bind within them. The inputs vary depending on when it is in development and in what cell a given gene is located, and the output is the “instruction” given to the basal transcription apparatus that determines whether the gene is to be silent, or active at a specified rate. If the gene encodes a transcription factor, the output leads to all the other cis-regulatory elements within which there are functional target sites for that transcription factor.

Regulatory Hardwiring: A Brief Overview of the Genomic Control Apparatus and its Causal Role in Development and Evolution

7 – Localization of Morphogenetic Determinants in Egg Cytoplasm

The present invention is directed to methods and compositions useful for altering the transcriptional expression of genes in eukaryotic cells. The invention employs novel antibody derivative molecules which function to recognize and bind to specific cis-regulatory DNA sequence elements of a eukaryotic gene. When two antibody derivative molecules are bound to adjacent cis-regulatory DNA sequence elements of a gene, those molecules may interact to form an antibody binding site which is capable of recognizing and binding to a transcription factor protein for the target gene, thereby affecting the functionality of that transcription factor protein and, in turn, the transcriptional activity of the gene. Also provided herein are isolated nucleic acids encoding the novel antibody derivative molecules of the present invention and expression vectors comprising those nucleic acids.

Eric H. Davidson

Papers

A new software package for predictive gene regulatory network modeling and redesign.

I – From Genome to Embryo: The Regulation of Gene Activity in Early Development

Regulatory Hardwiring: A Brief Overview of the Genomic Control Apparatus and its Causal Role in Development and Evolution

7 – Localization of Morphogenetic Determinants in Egg Cytoplasm

Method and compositions for controlling gene expression