Quantitative profiling of initiating ribosomes in vivo

Gao, Xiangwei; Wan, Ji; Liu, Botao; Ma, Ming; Shen, Ben; Qian, Shu‐Bing

doi:10.1038/nmeth.3208

Cited by 223 publications

(321 citation statements)

References 42 publications

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“…1B) with a mean footprint size surrounding 32 nucleotides (Fig. 1C), consistent with previous results obtained in mammalian cells or tissues (18)(19)(20)(21) as well as with ribosome size. Biological reproducibility for both RNA-Seq and Ribo-Seq was high ( Fig.…”

Section: Resultssupporting

confidence: 91%

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Atger

Gobet

Marquis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

208

287

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Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.circadian rhythms | ribosome profiling | mRNA translation | 5′-TOP sequences | TISU motifs L iving organisms on Earth are subjected to light-dark cycles caused by rotation of the Earth around the sun. To anticipate these changes, virtually all organisms have acquired a circadian timing system during evolution that allows a better adaptation to their environment. As a consequence, most aspects of their physiology are orchestrated in a rhythmic way by the circadian clock (from the Latin circa diem, meaning "about a day"), an endogenous and autonomous oscillator with a period of around 24 h (1, 2). Not surprisingly, perturbations of this clock in mammals lead to pathologies including psychiatric, metabolic, and vascular disorders (1,3,4). At the organismal scale, the oscillatory clockwork is organized in a hierarchal manner. Within the suprachiasmatic nuclei (SCN) of the hypothalamus, the "master clock" receives light input via the retina and communicates timing signals to "enslave" oscillators in peripheral organs (1, 2). The molecular oscillator consists of interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (5). These additional layers of regulation are largely coordinated by systemic cues originating from circadian clock and/or feeding-coordinated rhythmic metabolism, allowing the adjustment of the molecular clo...

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Section: Resultssupporting

confidence: 91%

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Atger

Gobet

Marquis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

208

287

View full text Add to dashboard Cite

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“…3), strongly suggesting evolutionary conservation of, not only the tail ORF, but also of the potential ribosome stalling at its 3' end. The AMD1 tail ribosome density peak is also present in ribosome profiling data obtained from cells treated with drugs that preferentially block ribosomes at sites of translation initiation 17,18 . This is characteristic of stalling sites and a similar ribosome peak can be observed for the well characterized stalling site at the end of the XBP1 coding region 19 (Extended Data Fig.…”

Section: Adometdc Catalyses the Decarboxylation Of S-adenosylmethionimentioning

confidence: 96%

AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation

Yordanova

Loughran

Zhdanov

et al. 2018

Nature

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“…Intriguingly, there have been hints that uORFs may be more common than initially believed. Translation can initiate (mostlikely using tRNA i Met ) at near cognate codons (NCCs)-sequences that differ from the canonical AUG start codon by one nucleotide (Zitomer et al 1984;Peabody 1989;Ivanov et al 2008Ivanov et al , 2011Kolitz et al 2009;Starck et al 2012;Kochetov et al 2013;Gao et al 2014). Thus, many NCC uORFs may be lying hidden in eukaryotic genomes.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

et al. 2017

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Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression.

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Quantitative profiling of initiating ribosomes in vivo

Cited by 223 publications

References 42 publications

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

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