CLIPSeqTools—a novel bioinformatics CLIP-seq analysis suite

Maragkakis, Manolis; Alexiou, Panagiotis; Nakaya, Tadashi; Mourelatos, Zissimos P.

doi:10.1261/rna.052167.115

Cited by 37 publications

(31 citation statements)

References 56 publications

(69 reference statements)

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“…The rates etc. of dissociation were all measured at 20°C and are slower compared to other published literature [5, 33]. Unlike previous reports [3–5] a recent report [33] showed the optimal concentration of EFG for ribosome splitting to be ~5μM.…”

Section: Resultsmentioning

confidence: 62%

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

et al. 2017

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Each cycle of translation initiation in bacterial cell requires free 50S and 30S ribosomal subunits originating from the post-translational dissociation of 70S ribosome from the previous cycle. Literature shows stable dissociation of 70S from model post-termination complexes by the concerted action of Ribosome Recycling Factor (RRF) and Elongation Factor G (EF-G) that interact with the rRNA bridge B2a/B2b joining 50S to 30S. In such experimental models, the role of full-length nascent protein was never considered seriously. We observed relatively slow release of full-length nascent protein from 50Sof post translation ribosome, and in that process, its toe prints on the rRNA in vivo and in in vitro translation with E.coli S30 extract. We reported earlier that a number of chemically unfolded proteins like bovine carbonic anhydrase (BCA), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lysozyme, ovalbumin etc., when added to free 70Sin lieu of the full length nascent proteins, also interact with identical RNA regions of the 23S rRNA. Interestingly the rRNA nucleotides that slow down release of the C-terminus of full-length unfolded protein were found in close proximity to the B2a/B2b bridge. It indicated a potentially important chemical reaction conserved throughout the evolution. Here we set out to probe that conserved role of unfolded protein conformation in splitting the free or post-termination 70S. How both the RRF-EFG dependent and the plausible nascent protein–EFG dependent ribosome recycling pathways might be relevant in bacteria is discussed here.

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Section: Resultsmentioning

confidence: 62%

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

et al. 2017

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“…We used CLIPSeqTools 39 , a bioinformatics suite that we created for analysis of CLIP-Seq datasets (accessible at: https://github.com/mnsmar/clipseqtools and http://mourelatos.med.upenn.edu/clipseqtools/tutorial/) and a Perl programming framework that we developed (M.M., P.A. and Z.M., manuscript in preparation; preprint available at: http://biorxiv.org/content/early/2015/11/03/019265).…”

Section: Methodsmentioning

confidence: 99%

Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm

Vourekas

Alexiou

Vrettos

et al. 2016

Nature

Self Cite

123

127

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The conserved Piwi family of proteins and piwi-interacting RNAs (piRNAs) play a central role in genomic stability, which is inextricably tied with germ cell formation, by forming ribonucleoproteins (piRNPs) that silence transposable elements (TEs)1. In Drosophila melanogaster and other animals, primordial germ cell (PGC) specification in the developing embryo is driven by maternal mRNAs and proteins that assemble into specialized mRNPs localized in the germ (pole) plasm at the posterior of the oocyte2,3. Maternal piRNPs, especially those loaded on Aubergine (Aub), a Piwi protein, are transmitted to the germ plasm to initiate transposon silencing in the offspring germline4–7. Transport of mRNAs to the oocyte by midoogenesis is an active, microtubule-dependent process8; mRNAs necessary for PGC formation are enriched in the germ plasm at late oogenesis via a diffusion and entrapment mechanism, whose molecular identity remains unknown8,9. Aub is a central component of germ granule RNPs, which house mRNAs in the germ plasm10–12 and interactions between Aub and Tudor are essential for the formation of germ granules13–16. Here we show that Aub-loaded piRNAs use partial base pairing characteristic of Argonaute RNPs to bind mRNAs randomly, acting as an adhesive trap that captures mRNAs in the germ plasm, in a Tudor-dependent manner. Strikingly, germ plasm mRNAs in Drosophilids are generally longer and more abundant than other mRNAs, suggesting that they provide more target sites for piRNAs to promote their preferential tethering in germ granules. Thus complexes containing Tudor, Aub piRNPs and mRNAs couple piRNA inheritance with germline specification. Our findings reveal an unexpected function for Piwi ribonucleoprotein complexes in mRNA trapping that may be generally relevant to the function of animal germ granules.

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“…The TL samples were obtained by the original authors (Maragkakis et al, 2016;Nakaya et al, 2013), and the authors provided only a brief description of the samples. Indeed, they only mention that the samples come from temporal surgical lobectomy of three unrelated individuals.…”

Section: Human Samplesmentioning

confidence: 99%

“…The Ago2-IP of the TL samples were performed using 2A8 Anti-Ago monoclonal antibody tethered to Protein A Dynabeads (Invitrogen), according to the original authors (Maragkakis et al, 2016). Further details can be found in the original article and in the BioProject NCBI database (PRJNA299324).…”

Section: Human Samplesmentioning

confidence: 99%

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A new member in the Argonaute crew: the mt-miRNAs

Pozzi¹,

Dowling²

2020

Preprint

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1Mutations within the mitochondrial genome have been linked to many diverse phenotypes. 2 Moreover, the effects of these mutations have been shown to differ across sexes and environments. 3 The mechanisms that explain the manifold array of mitochondrial genotypic effects on organismal 4 function, and their context-dependency, have however remained a mystery. Here, we present 5 evidence that mitochondria are involved in nuclear gene regulation via RNA interference; 6 transcribing mitochondrial (mt-)miRNAs that may repress the transcription of nuclear genes that 7 previously had no known involvement in mitochondrial function. Our findings uncover a new 8 mechanism by which mitochondria may shape the expression of animal life-histories and health 9 components; implying that the influence of the mitochondria in regulating organismal function 10 extends well beyond the process of energy production. 11 Introduction 12 Interest in mitochondrial biology is on the rise, with a growing number of studies 13 highlighting the complex role of the mitochondria in cell regulation (Picard, Wallace, and Burelle 14 2016; Sloan et al. 2018; Sprenger and Langer 2019). Among these, numerous studies have found 15 that sequence variation in the mitochondrial DNA (mtDNA) can affect the expression of a range 16 of life-history and health related traits, from fertility, to longevity and thermal tolerance (Lajbner 17 et al. 2018; Camus et al. 2017; Rand, Fry, and Sheldahl 2006; Song and Lewis 2008; Yee, Sutton, 18 and Dowling 2013; James and Ballard 2003). Furthermore, while it is well known that the mtDNA 19 can harbour loss-of-function mutations conferring mitochondrial disease in humans (Wallace 20 2018), emerging studies implicate mtDNA mutations in a range of other late-onset diseases not 21 previously linked to mitochondrial function (Hudson et al. 2014). For example, Hopkins et al. 22 (2017) recently reported an association between the frequency and type of mtDNA mutations and aggressiveness of prostate cancer. Furthermore, the phenotypic effects of these mtDNA mutations 1 appear to be routinely moderated by the nuclear genetic background alongside which the mtDNA 2 mutations are co-expressed (Hill et al. 2018), suggesting a broad role for intergenomic regulation 3 ("mitonuclear communication") involving exchange of proteins, metabolites and genetic products 4 between genomes (Wu et al. 2019; Moriyama, Koshiba, and Ichinohe 2019; Zhu, Ingelmo, and 5 Rand 2014). The mechanistic basis of the molecular interactions that underpin mitonuclear 6 regulation of cellular and organismal function, however, remains elusive. 7 In 2019, Kopinski et al. provided new insights into how the mitochondria communicate 8 with the nucleus, reporting a key role for mitochondrial metabolites and subcellular redox levels. 9The authors found that variation in the level of intracellular mtDNA heteroplasmy (i.e. the 10 frequency of normal to mutant mtDNA molecules) modulates mitochondrial metabolites, 11 influencing the abundance of substrate necessary for...

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CLIPSeqTools—a novel bioinformatics CLIP-seq analysis suite

Cited by 37 publications

References 56 publications

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm

A new member in the Argonaute crew: the mt-miRNAs

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