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Tales around the clock: Poly(A) tails in circadian gene expression

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Circadian rhythms are ubiquitous time‐keeping processes in eukaryotes with a period of ~24 hr. Light is perhaps the main environmental cue (zeitgeber) that affects several aspects of physiology and behaviour, such as sleep/wake cycles, orientation of birds and bees, and leaf movements in plants. Temperature can serve as the main zeitgeber in the absence of light cycles, even though it does not lead to rhythmicity through the same mechanism as light. Additional cues include feeding patterns, humidity, and social rhythms. At the molecular level, a master oscillator orchestrates circadian rhythms and organizes molecular clocks located in most cells. The generation of the 24 hr molecular clock is based on transcriptional regulation, as it drives intrinsic rhythmic changes based on interlocked transcription/translation feedback loops that synchronize expression of genes. Thus, processes and factors that determine rhythmic gene expression are important to understand circadian rhythms. Among these, the poly(A) tails of RNAs play key roles in their stability, translational efficiency and degradation. In this article, we summarize current knowledge and discuss perspectives on the role and significance of poly(A) tails and associating factors in the context of the circadian clock. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > 3′ End Processing
Poly(A) tails in co‐transcriptional and posttranscriptional modifications of RNA. (a) mRNA modifications. RNA polymerase II (RNAP II) transcribes DNA (1) and the nascent transcript (red line) is capped (2). The first intron (orange line) is transcribed (3) and splicing joins the two exons releasing a lariat (4). Editing takes place (5) and upon transcription of the AAUAAA sequence (black line) cleavage at the polyadenylation site (p(A)) is shown (6). The transcript bears chemical modifications, such as methylation of adenine (m6A), shown as blue dot (7), and the mature mRNA exits the nucleus (8) and is translated in the cytoplasm. The degradation of mRNA starts with the shortening of the poly(A) tail by deadenylases (red packman), a mechanism that may be mediated by hybridization of the miRNA (shown as light green line) and miRISC binding on the transcript (9). (b) rRNA polyadenylation in the diurnal production of ribosomes. RNA polymerase I (RNAP I) transcribes DNA synthesizing 18S (I), 5.8S (II) and 28S rRNAs (III), shown as magenta, green and cyan lines, respectively. Pre‐rRNA is constitutively synthesized in excess throughout the day. High ribosomal protein synthesis during the active/dark phase, rRNAs is incorporated to complete ribosomes exported to the cytoplasm (IV). Due to low ribosomal protein synthesis during the resting/light phase, the excess of rRNA that is not assembled into functional ribosomes are polyadenylated and degraded by EXOSC10 (olive pacman) in the nucleus (V). For simplicity, PAPD5 that polyadenylates the transcripts is not shown. Gray lines indicate the 5′ and the two internal spacers (the 3′ spacer is not shown). Based on a previously described model (Sinturel et al., ). (c) Alternative polyadenylation. Selection between polyadenylation sites 1 or 2 (p(A)1 or p(A)2) results in different transcripts. Clocks and thermometers indicate steps that subject to circadian and temperature changes, respectively
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A simplified transcription‐focused part of the circadian system. Solar light, temperature, and other diverse cues (whirlwind) interact with body sensors (windmill sails). The latter transmit the interweaved information to the central oscillator/clock (central gear), which generates outputs and physiological responses (not shown). The oscillator activates transcription, processing, and stability of circadian‐controlled RNAs, including core clock mRNAs, circadian controlled mRNAs and rRNAs (collectively shown as water in the bucket; capped and noncapped lines show polyadenylated mRNA and rRNA, respectively). Co‐transcriptional and posttranscriptional modifications (depicted as gears (Nohales & Kay, )) regulate the stability of mRNAs and determine the levels of oscillating RNAs, reflected on the balance between transcription and decay rates (depicted as water input by the tap and water output, respectively (Ross, )) mediated by degradation factors (pacman), thus contributing to the generation of the 24‐hr molecular clock. For simplicity, only solar light (sun) and temperature (thermometer) are depicted as inputs; “…” indicates other inputs (e.g., feeding patterns, social rhythms, etc.). The windmill sails represent any intermediate signaling sensor that interacts with the central oscillator (e.g., the retina that signals the light changes to suprachiasmatic nucleus [SCN]). Sinusoidal curves represent main components and processes under circadian regulation. The axis between the windmill and the central oscillator gear is shown as a dashed line to indicate that the core oscillator does not depend solely on external cues to maintain rhythmicity
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RNA Processing > 3′ End Processing
RNA Turnover and Surveillance > Regulation of RNA Stability

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