David Bartel
Salem
As seen in:
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My passions: Advancing my knowledge and advancing others. Movies, Video Games, TV Shows, Entertainment in general through a critical lens.
Articles by David Bartel
The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation
Abstract MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form complexes that down-regulate target RNAs, including messenger RNAs from most human genes1,2,3. Within each complex, the miRNA pairs to target RNAs, and AGO provides effector function while also protecting the miRNA from cellular nucleases2,3,4,5. Although much is known about miRNA-directed gene regulation, less is known about how miRNAs themselves are regulated.
The G3BP stress-granule proteins reinforce the integrated stress response translation programme - Nature Cell Biology
Abstract When mammalian cells are exposed to stress, they co-ordinate the condensation of stress granules (SGs) through the action of proteins G3BP1 and G3BP2 (G3BPs) and, simultaneously, undergo a massive reduction in translation. Although SGs and G3BPs have been linked to this translation response, their overall impact has been unclear. Here we investigate the question of how, and indeed whether, G3BPs and SGs shape the stress translation response.
PAL-AI reveals genetic determinants that control poly(A)-tail length during oocyte maturation, with relevance to human fertility - Nature Communications
Abstract In oocytes of mammals and other animals, gene regulation is mediated primarily through changes in poly(A)-tail length. Here, we introduce PAL-AI, an integrated neural network machine-learning model that accurately predicts tail-length changes in maturing oocytes of frogs and mammals.
Derepression of a single microRNA target causes female infertility in mice
Abstract The miR-200a and miR-200b families control mouse ovulation and are essential for female fertility. The ZEB1 transcription factor is a conserved target of both families and has been implicated as a key player in female fertility at multiple levels. Using gene-edited mice that express a miR-200a/b-resistant form of Zeb1, we found that derepression of Zeb1 in the female pituitary caused decreased production of luteinizing hormone and anovulatory infertility.
Functional microRNA targeting without seed pairing
Abstract MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to serve as guides, directing binding to partially complementary sites in mRNAs, ultimately causing post-transcriptional repression. Complementarity to the miRNA seed region (miRNA nucleotides 2–7) is typically both necessary and sufficient for repression. Here, we investigate unusual sites with extensive complementarity to the miRNA 3′ region (nucleotide 9 and onwards) but without complementarity to the seed.
PAL-AI reveals genetic determinants that control poly(A)-tail length during oocyte maturation with relevance to human fertility
Abstract In oocytes of mammals and other animals, gene regulation is mediated primarily through changes in poly(A)-tail length. Here, we introduce PAL-AI, an integrated neural network machine-learning model that accurately predicts tail-length changes in maturing oocytes of frogs and mammals.
Nuclear release of eIF1 restricts start-codon selection during mitosis - Nature
Abstract Regulated start-codon selection has the potential to reshape the proteome through the differential production of upstream open reading frames, canonical proteins, and alternative translational isoforms1,2,3. However, conditions under which start codon selection is altered remain poorly defined. Here, using transcriptome-wide translation-initiation-site profiling4, we reveal a global increase in the stringency of start-codon selection during mammalian mitosis.
The guide-RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex
Highlights • Sequence of guide RNA can alter slicing rate of fully paired substrate by 250-fold • Sequences that cause more rapid slicing direct more efficient RNAi in cells • Strong central pairing imparts tolerance for mismatches to the guide 3′ region • This tolerance is attributable to more fully populating the slicing conformation Summary The RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target...
Widespread destabilization of C. elegans microRNAs by the E3 ubiquitin ligase EBAX-1
Abstract MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form complexes that direct mRNA repression. miRNAs are also the subject of regulation. For example, some miRNAs are destabilized through a pathway in which pairing to specialized transcripts recruits the ZSWIM8 E3 ubiquitin ligase, which polyubiquitinates AGO, leading to its degradation and exposure of the miRNA to cellular nucleases. Here, we found that 22 miRNAs in C.
The guide RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex
Abstract The RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target RNAs complementary to the guide. We find that for different guide-RNA sequences, slicing rates of perfectly complementary, bound targets can be surprisingly different (>250-fold range), and that faster slicing confers better knockdown in cells.
Control of poly(A)-tail length and translation in vertebrate oocytes and early embryos
Highlights • UUUUA, influenced by contextual features, specifies most cytoplasmic polyadenylation • Stage-specific 3′ UTR elements drive waves of tail-length shortening in embryos • UUUUA and C-rich motifs can direct tail-length-independent translational repression • Tail-length control is conserved in oocytes of frogs, mice, and humans Summary During oocyte maturation and early embryogenesis, changes in mRNA poly(A)-tail lengths strongly influence translation, but how these tail-length...
Control of poly(A)-tail length and translation in vertebrate oocytes and early embryos
Abstract During oocyte maturation and early embryogenesis, changes in mRNA poly(A)-tail lengths strongly influence translation, but how these tail-length changes are orchestrated has been unclear. Here, we performed tail-length and translational profiling of mRNA reporter libraries (each with millions of 3ʹ-UTR sequence variants) in frog oocytes and embryos, and fish embryos.
The guide RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex
Abstract The RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target RNAs complementary to the guide. We find that for different guide-RNA sequences, slicing rates of perfectly paired, bound targets can be surprisingly different (>250-fold range), and that faster slicing confers greater knockdown efficacy in cells. Four sequence determinants underlie much of this variation in slicing rates.
Endogenous transcripts direct microRNA degradation in Drosophila, and this targeted degradation is required for proper embryonic development
Method details Drosophila S2 cell transfection and genome editing For transfection of S2 cells, effectene (Qiagen) was used according to the manufacturer’s protocol, starting with cells that had been seeded 24 h earlier at a density of 2 million cells/mL (counted with a Countess cell automated counter, Invitrogen).
A statistical approach for identifying primary substrates of ZSWIM8-mediated microRNA degradation in small-RNA sequencing data
Abstract Background: One strategy for identifying targets of a regulatory factor is to perturb the factor and use high-throughput RNA sequencing to examine the consequences. However, distinguishing direct targets from secondary effects and experimental noise can be challenging when confounding signal is present in the background at varying levels.
The biochemical basis for the cooperative action of microRNAs
We need more data on the risks mining poses to ocean life and ecosystems.
MicroRNA Clustering Assists Processing of Suboptimal MicroRNA Hairpins through the Action of the ERH Protein
Highlights • miRNA hairpins can assist in processing neighboring hairpins in mammalian cells • The assistance scales with Microprocessor recognition of the linked helper hairpin • Processing of the recipient hairpin is usually realized after processing of the helper • ERH, which copurifies with Microprocessor, enables cluster assistance Summary Microprocessor initiates the processing of microRNAs (miRNAs) from the hairpin regions of primary transcripts (pri-miRNAs).
MicroRNAs Cause Accelerated Decay of Short-Tailed Target mRNAs
Highlights • miRNAs cause accelerated decay of short-tailed target molecules • This accelerated decay largely prevents accumulation of short-tailed target mRNAs • miRNAs are similarly effective on short-lived and long-lived target mRNAs • In 3T3 cells, miRNA effects on translation are negligible, even for nascent mRNAs Summary MicroRNAs (miRNAs) specify the recruitment of deadenylases to mRNA targets.
Excised linear introns regulate growth in yeast
Abstract Spliceosomal introns are ubiquitous non-coding RNAs that are typically destined for rapid debranching and degradation. Here we describe 34 excised introns in Saccharomyces cerevisiae that—despite being rapidly degraded in log-phase growth—accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, which is a key integrator of growth signalling.
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain
Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA.
Metazoan MicroRNAs
High-throughput sequencing of small RNAs has transformed miRNA gene discovery (Lu et al., 2005xElucidation of the small RNA component of the transcriptome. Lu, C., Tej, S.S., Luo, S., Haudenschild, C.D., Meyers, B.C., and Green, P.J. Science. ; 309: 1567–1569 Google ScholarSee all References, Ruby et al., 2006xLarge-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans.
Expanded identification and characterization of mammalian circular RNAs
To identify circRNAs from RNA-seq data, we developed the following computational pipeline (Figure 1B). We first mapped all the RNA-seq reads to the genome using Bowtie in single-end mode, allowing ?2 mismatches. Then we used BLAT to find partial alignment of the unmapped reads.
A Seed Mismatch Enhances Argonaute2-Catalyzed Cleavage and Partially Rescues Severely Impaired Cleavage Found in Fish
The RNAi pathway provides both innate immunity and efficient gene-knockdown tools in many eukaryotic species, but curiously not in zebrafish. We discovered that RNAi is less effective in zebrafish at least partly because Argonaute2-catalyzed mRNA slicing is impaired.
Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability
To use the Enhanced view of this article, please enable JavaScript on in your browser and refresh the page. ArticleWidespread Influence of 3?-End Structures on Mammalian mRNA Processing and Stability Xuebing WuxXuebing WuSearch for articles by this authorAffiliationsHoward Hughes Medical Institute and Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USADepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, David P. BartelxDavid P.
RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria
Many cellular RNAs contain regions that fold into stable structures required for function. Both Watson−Crick and noncanonical interactions can play important roles in forming these structures. An intriguing noncanonical structure is the RNA G-quadruplex (RG4), a four-stranded structure containing two or more layers of G-quartets, in which the Watson–Crick face of each of four G residues pairs to the Hoogsteen face of the neighboring G residues.
Expanded identification and characterization of mammalian circular RNAs
To identify circRNAs from RNA-seq data, we developed the following computational pipeline (Figure 1B). We first mapped all the RNA-seq reads to the genome using Bowtie in single-end mode, allowing ≤2 mismatches. Then we used BLAT to find partial alignment of the unmapped reads.
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