RNA interactome capture provides new insights into embryo development

Two recent reports have determined the RNA interactome of Drosophila melanogaster embryos, revealing hundreds of novel RBPs. One of this works study the plasticity of the RBPome during development by comparing RNA-binding activities in early and late embryo. This analysis reveal the high adaptation capacity of the RBPome to physiological changes.

Nat Commun. 2016 Jul 5;7:12128. doi: 10.1038/ncomms12128.

Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila.

The maternal-to-zygotic transition (MZT) is a process that occurs in animal embryos at the earliest developmental stages, during which maternally deposited mRNAs and other molecules are degraded and replaced by products of the zygotic genome. The zygotic genome is not activated immediately upon fertilization, and in the pre-MZT embryo post-transcriptional control by RNA-binding proteins (RBPs) orchestrates the first steps of development. To identify relevant Drosophila RBPs organism-wide, we refined the RNA interactome capture method for comparative analysis of the pre- and post-MZT embryos. We determine 523 proteins as high-confidence RBPs, half of which were not previously reported to bind RNA. Comparison of the RNA interactomes of pre- and post-MZT embryos reveals high dynamicity of the RNA-bound proteome during early development, and suggests active regulation of RNA binding of some RBPs. This resource provides unprecedented insight into the system of RBPs that govern the earliest steps of Drosophila development.

Genome Res. 2016 Jul;26(7):1000-9. doi: 10.1101/gr.200386.115. Epub 2016 Apr 28.

The mRNA-bound proteome of the early fly embryo.

Early embryogenesis is characterized by the maternal to zygotic transition (MZT), in which maternally deposited messenger RNAs are degraded while zygotic transcription begins. Before the MZT, post-transcriptional gene regulation by RNA-binding proteins (RBPs) is the dominant force in embryo patterning. We used two mRNA interactome capture methods to identify RBPs bound to polyadenylated transcripts within the first 2 h of Drosophila melanogaster embryogenesis. We identified a high-confidence set of 476 putative RBPs and confirmed RNA-binding activities for most of 24 tested candidates. Most proteins in the interactome are known RBPs or harbor canonical RBP features, but 99 exhibited previously uncharacterized RNA-binding activity. mRNA-bound RBPs and TFs exhibit distinct expression dynamics, in which the newly identified RBPs dominate the first 2 h of embryonic development. Integrating our resource with in situ hybridization data from existing databases showed that mRNAs encoding RBPs are enriched in posterior regions of the early embryo, suggesting their general importance in posterior patterning and germ cell maturation.

The new (dis)order in RNA biology

The current paradigm of RNA-binding proteins is that they contain regions, or domains, that fold tightly into an ordered interaction platform that mediate RNA binding. In this review, we describe how this paradigm has been challenged by studies showing that other, hitherto neglected regions in RNA-binding proteins, which in spite of being intrinsically disordered, can play key functional roles in protein-RNA interactions. Proteins harbouring such disordered regions are involved in virtually every step of RNA regulation and, in some instances, have been implicated in disease. Based on exciting recent discoveries that indicate their unexpectedly pervasive role in RNA binding, we propose that the systematic study of disordered regions within RNA-binding proteins will shed light on poorly understood aspects of RNA biology and their implications in health and disease.

FULL PAPER HERE

The RBPome of yeast (S. cerevisiae) and worms (C. elegans) uncovered

Recently, two independents works published in Nature Com and NSMB have shown the unexpected complexity of the repertoire of RNA-binding proteins in both S. cerevisiae and C. Elegans. Strikingly, metabolic enzymes and other enzymatic cores arise as enigmatic RNA-binders from yeast to human, suggesting either surprising and conserved roles of these proteins in post-transcriptional control of gene expression or a widespread function of RNA as regulator of enzymatic activities.

For more details visit:

The RNA-binding proteomes from yeast to man harbour conserved enigmRBPs.

Benedikt M. Beckmann, Rastislav Horos, Bernd Fischer, Alfredo Castello, Katrin Eichelbaum, Anne-Marie Alleaume, Thomas Schwarzl, Tomaž Curk, Sophia Foehr, Wolfgang Huber, Jeroen Krijgsveld & Matthias W. Hentze

http://www.nature.com/ncomms/2015/151203/ncomms10127/full/ncomms10127.html

Conserved mRNA-binding proteomes in eukaryotic organisms

Ana M Matia-González, Emma E Laing & André P Gerber

http://www.nature.com/nsmb/journal/v22/n12/full/nsmb.3128.html

 

Tiny perfection

What makes so special to HIV is its capacity to attack the generals of the immunological system: the Lymphocytes T CD4+. These cells coordinate the immune response, sending orders and messages to the soldiers in form of cytokines and chemokines . Without “generals”, the army is condemned to defeat. HIV also has “Achilles heel”… For example, antiretroviral compounds can inhibit the viral functions required for its multiplication in the infected cell, keeping the levels of virus low and allowing the immune system to work. However, its very challenging to eliminate this virus, because it constantly changes its “face” (glycoproteins) to hide from the immune system. HIV mutates very rapidly (1 mutantion each 10,000 nucleotides) allowing fast adaptation against environmental pressures, such as antivirals. In addition, HIV can hide inside the cell in a latent form, which can be activated again when the proper stimulus arrives. We are still far to understand the mechanisms underlying the transitions between the active state and the latency…   This could be the key for the elimination of HIV.

Here you will see the images about HIV and infected cells released in Cell-Press: http://www.cell.com/pictureshow/hiv

HIV virion099

HIV virion                                                      HIV maturation

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HIV leaving the infected cell                       Infected dendritic cell and lymphocytes