Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Menet, Jérôme S.; Rodriguez, Joseph; Abruzzi, Katharine C.; Rosbash, Michael

doi:10.7554/elife.00011

Cited by 295 publications

(444 citation statements)

References 49 publications

Supporting

Mentioning

411

Contrasting

Unclassified

Order By: Relevance

“…Although two studies concluded that transcriptional regulation constitutes the main origin of rhythm mRNA accumulation (ref. 34 and this study), two others concluded that this origin is mainly posttranscriptional (7,35). Interestingly, analysis of these data through a new approachtaking into account mRNA degradation-led to the observation that ∼70% of transcripts are not subjected to posttranscriptional regulation, in accordance with our conclusion (36).…”

Section: Translation Efficiency Is Regulated During the Diurnal Cyclesupporting

confidence: 79%

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.

217

287

View full text Add to dashboard Cite

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...

show abstract

Section: Translation Efficiency Is Regulated During the Diurnal Cyclesupporting

confidence: 79%

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.

217

287

View full text Add to dashboard Cite

show abstract

“…In addition, there are substantial differences between the expression levels and the cycling patterns of nascent and mature transcripts (9,13). For example, 193 of the 263 fly head mRNAs with cycling expression had lower amplitudes or even flat expression at the nascent RNA levels (9).…”

mentioning

confidence: 99%

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

Xiao

Rosbash

2016

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

Self Cite

View full text Add to dashboard Cite

Circadian rhythms in metazoan eukaryotes are controlled by an endogenous molecular clock. It functions in many locations, including subsets of brain neurons (clock neurons) within the central nervous system. Although the molecular clock relies on transcription/translation feedback loops, posttranscriptional regulation also plays an important role. Here, we show that the abundant Drosophila melanogaster microRNA mir-276a regulates molecular and behavioral rhythms by inhibiting expression of the important clock gene timeless (tim). Misregulation of mir-276a in clock neurons alters tim expression and increases arrhythmicity under standard constant darkness (DD) conditions. mir-276a expression itself appears to be light-regulated because its levels oscillate under 24-h light-dark (LD) cycles but not in DD. mir-276a is regulated by the transcription activator Chorion factor 2 in flies and in tissue-culture cells. Evidence from flies mutated using the clustered, regularly interspaced, short palindromic repeats (CRISPR) tool shows that mir-276a inhibits tim expression: Deleting the mir276a-binding site in the tim 3′ UTR causes elevated levels of TIM and ∼50% arrhythmicity. We suggest that this pathway contributes to the more robust rhythms observed under light/dark LD conditions than under DD conditions. microRNA | circadian rhythms | light regulation | CRISPR

show abstract

“…Overlapping list represented 65% of the list obtained with one probe and 83% of the list obtained with the other one. By comparing this gene list to available data in the literature such as the list of rhythmic mRNA in the mouse pituitary 13 or the mRNA whose rhythm is post-transcriptionally controlled in the liver of mice, 15 we achieved significant recovery rates of 18 and 27%, respectively. These rates are probably underestimated since they come from the comparison of gene lists obtained in different structures and species.…”

mentioning

confidence: 99%

“…However, data from mouse liver demonstrate poor correlation between the activation of a promoter and the amount of the corresponding transcript for genes that are rhythmic at the steady-state level. 15 Actually, with the development of high-throughput sequencing, results obtained in the last years indicate that approximately 43% of the mammalian genome is rhythmic and analysis of circadian nascent RNA has allowed to show that less than 30 % of circadian mRNA are regulated by de novo transcription, suggesting that post-transcriptional regulation contributes mostly to rhythmic mRNA expression (Fig. 1).…”

mentioning

confidence: 99%

“…1). [15][16][17][18][19] Much of what we initially knew about post-transcriptional regulation came from studies of fungi, plants and flies (For a review see 20 ), but circadian post-transcriptional mechanisms involved in rhythmic control of mRNA expression have now also been reported in mammals at many different levels (For a review see ref. 21), such as RNA splicing, poly-adenylation, mRNA stability, mRNA cytoplasmic export and RNA nuclear retention (Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Paraspeckles as rhythmic nuclear mRNA anchorages responsible for circadian gene expression

Torres

Becquet

Blanchard

et al. 2017

Nucleus

View full text Add to dashboard Cite

Circadian clocks regulate rhythmic gene expression levels by means of mRNA oscillations that are mainly driven by post-transcriptional regulation. We identified a new post-transcriptional mechanism, which involves nuclear bodies called paraspeckles. Major components of paraspeckles including the long noncoding RNA Neat1, which is the structural component, and its major protein partners, as well as the number of paraspeckles, follow a circadian pattern in pituitary cells. Paraspeckles are known to retain within the nucleus RNAs containing inverted repeats of Alu sequences. We showed that a reporter gene in which these RNA duplex elements were inserted in the 3'-UTR region displayed a circadian expression. Moreover, circadian endogenous mRNA associated with paraspeckles lost their circadian pattern when paraspeckles were disrupted. This work not only highlights a new paraspeckle-based post-transcriptional mechanism involved in circadian gene expression but also provides the list of all mRNA associated with paraspeckles in the nucleus of pituitary cells.

show abstract

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Cited by 295 publications

References 49 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

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

Paraspeckles as rhythmic nuclear mRNA anchorages responsible for circadian gene expression

Contact Info

Product

Resources

About