Top 8 Biorxiv Papers Today in Molecular Biology


2.157 Mikeys
#1. DDX3 depletion selectively represses translation of structured mRNAs
Lorenzo Calviello, Srivats Venkataramanan, Karol J Rogowski, Emanuel Wyler, Malvika Tejura, Bao Thai, Jacek Krol, Witold Filipowicz, Markus Landthaler, Stephen N Floor
DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Its yeast ortholog Ded1 controls the translation of nearly all mRNAs, whereas DDX3 is thought to regulate only a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds most expressed mRNAs, depletion of DDX3 affects the translation level of only a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosome, placing it immediately adjacent to the mRNA entry channel and translation factor eIF4B. Translation changes caused by depleting DDX3 levels or through chemical inhibition mimicking a dominant negative allele are different. Taken together, our data defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and...
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thparietallobe: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
IgorUlitsky: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
jdf_ev: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
dev2death: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
LizzieBillingt1: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
Orel_Miz: RT @biorxivpreprint: DDX3 depletion selectively represses translation of structured mRNAs https://t.co/LfSwU0S31D #bioRxiv
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Authors: 10
Total Words: 0
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2.036 Mikeys
#2. Efficient and specific oligo-based depletion of rRNA
Amelie J Kraus, Benedikt G Brink, Tim Nicolai Siegel
In most organisms, ribosomal RNA (rRNA) contributes to >85% of total RNA. Thus, to obtain useful information from RNA-sequencing (RNA-seq) analyses at reasonable sequencing depth, typically, mature polyadenylated transcripts are enriched or rRNA molecules are depleted. Targeted depletion of rRNA or other highly abundant transcripts is particularly useful when studying transcripts lacking a poly(A) tail, such as some non-coding RNAs (ncRNAs), most bacterial RNAs and partially degraded or immature transcripts. While several commercially available kits allow effective rRNA depletion, their efficiency relies on a high degree of sequence homology between oligonucleotide probes and the target RNA. This restricts the use of such kits to a limited number of organisms with conserved rRNA sequences. In this study we describe the use of biotinylated oligos and streptavidin-coated paramagnetic beads for the efficient and specific depletion of trypanosomal rRNA. Our approach reduces the levels of the most abundant rRNA transcripts to less than...
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grawoig: RT @biorxivpreprint: Efficient and specific oligo-based depletion of rRNA https://t.co/G0QntgXZdq #bioRxiv
ilyavkirov: RT @biorxivpreprint: Efficient and specific oligo-based depletion of rRNA https://t.co/G0QntgXZdq #bioRxiv
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Authors: 3
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2.019 Mikeys
#3. A new cryo-EM system for electron 3D crystallography by eEFD
Koji Yonekura, Tetsuya Ishikawa, Saori Maki-Yonekura
A new cryo-EM system has been developed and investigated for use in protein electron 3D crystallography. The system provides parallel illumination of a coherent 300 kV electron beam to a sample, filters out energy-loss electrons through the sample with an in-column energy filter, and allows rotational data collection on a fast camera. It also possesses motorized cryo-sample loading and automated liquid-nitrogen filling for cooling of multiple samples. To facilitate its use, we developed GUI programs for efficient operation and accurate structure analysis. Here we report on the performance of the system and first results for thin 3D crystals of the protein complexes, catalase and membrane protein complex ExbBD. Data quality is remarkably improved with this approach, which we name eEFD (electron energy-filtered diffraction of 3D crystals), compared with those collected at 200 kV without energy filtration. Key advances include precise control of the microscope and recordings of lens fluctuations, which the programs process and...
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biorxivpreprint: A new cryo-EM system for electron 3D crystallography by eEFD https://t.co/fmGHJgqgdz #bioRxiv
cryoEM_Papers: A new cryo-EM system for electron 3D crystallography by eEFD https://t.co/YefHl48SIy
PabloINik: RT @biorxivpreprint: A new cryo-EM system for electron 3D crystallography by eEFD https://t.co/fmGHJgqgdz #bioRxiv
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Authors: 3
Total Words: 8728
Unqiue Words: 2414

2.007 Mikeys
#4. Codon Optimality Confers GC-Rich-Induced Stability to mRNAs in Humans
Fabian Hia, Sheng Fan Yang, Yuichi Shichino, Masanori Yoshinaga, Yasuhiro Murakawa, Alexis Vandenbon, Akira Fukao, Toshinobu Fujiwara, Markus Landthaler, Tohru Natsume, Shungo Adachi, Shintaro Iwasaki, Osamu Takeuchi
Codon optimality has been implicated as a major factor contributing to mRNA stability in yeast. However, the presence of codon optimality mediated decay has been unclear in humans. Here we show that human cells possess a mechanism to modulate RNA stability via codon optimality with a unique codon bias different from that of yeast. We performed dimensionality reduction analysis of genome wide codon frequencies and found that codons could be clustered into two distinct groups, codons with A or T at the third base position (AT3) and codons with either G or C at the third base position (GC3). Quantifying codon bias and subsequently gene optimality showed that increased GC3 content entails proportionately higher GC content which in turn confers stability to mRNA transcripts. Agreement of our codon optimality derived metric and ribosome occupancies across mRNAs determined from ribosome profiling suggests that codon optimality affects ribosome occupancy. This system was verified by measuring the stabilities of codon optimized and...
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biorxivpreprint: Codon Optimality Confers GC-Rich-Induced Stability to mRNAs in Humans https://t.co/bizpJNYqbl #bioRxiv
razoralign: RT @biorxivpreprint: Codon Optimality Confers GC-Rich-Induced Stability to mRNAs in Humans https://t.co/bizpJNYqbl #bioRxiv
kurai_yousei: RT @biorxivpreprint: Codon Optimality Confers GC-Rich-Induced Stability to mRNAs in Humans https://t.co/bizpJNYqbl #bioRxiv
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Authors: 13
Total Words: 9741
Unqiue Words: 2910

1.993 Mikeys
#5. Prenatal Exposure to Environmental Chemicals Modulates Serum Phospholipids in Newborn Infants, Increasing Later Risk of Type 1 Diabetes
Aidan McGlinchey, Tim Sinioja, Santosh Lamichhane, Johanna Bodin, Heli Siljander, Dawei Geng, Cecilia Carlsson, Daniel Duberg, Jorma Ilonen, Suvi M. Virtanen, Hubert Dirven, Hanne F. Bentsen, Karin Zimmer, Unni C. Nygaard, Matej Oresic, Mikael Knip, Tuulia Hyotylainen
In the last decade, the increasing incidence of type 1 diabetes (T1D) stabilized in Finland, coinciding with tighter regulation of per- and polyfluoroalkyl substances (PFAS). Here we applied lipidomics and quantification of PFAS to examine their effect, during pregnancy, on lipid-related markers of T1D risk in children. In a well-characterized mother-infant cohort (264 pairs), high PFAS exposure during pregnancy associated with decreased phospholipids in the offspring. This association was exacerbated with increased human leukocyte antigen-conferred risk of T1D in infants. Their lipid profiles proved similar to those observed in earlier studies in young children progressing to T1D later in life. Exposure to a single PFAS compound or a PFAS-containing mixture of organic pollutants in non-obese diabetic mice resulted in their offspring seeing a similar decrease in phospholipids, with early signs of insulitis. Our findings suggest that high PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in children.
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Sample Sizes : [8, 5]
Authors: 17
Total Words: 13115
Unqiue Words: 4203

1.992 Mikeys
#6. De novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus for molecular analysis of aestivation
Naoki Yoshida, Chikara Kaito
The molecular mechanisms of aestivation, a state of dormancy that occurs under dry conditions at ordinary temperature, are not yet clarified. Here, we report the first de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus, which aestivates for 6-10 months during the hot and dry season. Polyadenylated RNA from tissues was sequenced to 75,320,390 paired-end reads, and the de novo assembly generated 101,682 transcripts. Of these, 100,093 transcripts had open reading frames encoding more than 25 amino acids. BLASTx analysis against the Uniprot Xenopus tropicalis protein database revealed 64,963 transcripts having little homology with an E value higher than 1E-5 and 8,147 transcripts having no homology, indicating that the African bullfrog has many novel genes that are absent in X. tropicalis. The other 28,570 transcripts had homology with an E value lower than 1E-5 for which molecular functions were estimated by gene ontology (GO) analysis and found to contain the aestivation-related genes conserved among other...
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Authors: 2
Total Words: 6628
Unqiue Words: 2436

1.991 Mikeys
#7. Cytosolic termini of the FurE transporter regulate endocytosis, pH-dependent gating and specificity
Georgia F Papadaki, George Lamprinidis, Andreas Zamanos, Emmanuel Mikros, George Diallinas
FurE, a member of the NCS1 family, is an Aspergillus nidulans transporter specific for uracil, allantoin and uric acid. Recently we showed that C- or N-terminally truncated FurE versions are blocked for endocytosis and, surprisingly, show modified substrate specifities. Bifluorescence complementation assays and genetic analyses supported that the C- and N-termini interact dynamically and through this interaction regulate selective substrate translocation. Here we functionally dissect and delimit distinct motifs crucial for endocytosis, transport activity, substrate specificity and folding, in both cytosolic termini of FurE. Subsequently, we obtain novel genetic and in silico evidence supporting that the molecular dynamics of specific N- and C-terminal regions affect allosterically the gating mechanism responsible for substrate selection, via pH-dependent interactions with other internal cytosolic loops and membrane lipids. Our work shows that elongated cytoplasmic termini, acquired through evolution mostly in eukaryotic...
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Authors: 5
Total Words: 14953
Unqiue Words: 4376

1.979 Mikeys
#8. Cross-talk between m6A and m1A regulators, YTHDF2 and ALKBH3 fine-tunes mRNA expression
Nga Lao, Niall Barron
The recently re-discovered interest in N6-methyl adenosine (m6A) - one of more than a hundred modifications found on eukaryotic mRNA (known as epi-transcriptomic codes) - is currently one of the most topical areas in science. The m6A methylation impacts on all aspects of cellular RNA metabolism and several physiological processes. Although less abundant than the m6A epitranscriptomic mark, the m1A methylation has recently also attracted interest due to its dynamic nature in response to physiological changes. We investigated the role of the YTH domain-containing m6A reader protein family and the m1A eraser ALKBH3 on the expression of a transgene in mammalian cells. We present the first evidence that expression of a transgene is subjected to co-ordinated regulation by both m6A and m1A regulators. In addition, we provide genetic data implicating that the m6A reader YTHDF2 can read m1A site. Furthermore, we show that the m1A eraser ALKBH3 is a target of m1A methylation.
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ZivShulman: RT @biorxivpreprint: Cross-talk between m6A and m1A regulators, YTHDF2 and ALKBH3 fine-tunes mRNA expression https://t.co/DtRkZjk0dk #bioR…
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