Transcriptional buffering and 3ʹUTR lengthening are shaped during human neurodevelopment by shifts in mRNA stability and microRNA load

Mufteev, Marat; Rodrigues, Deivid C.; Yuki, Kyoko E.; Narula, Ashrut; Wei, Wei; Piekna, Alina; Liu, Jiajie; Pasceri, Peter; Rissland, Olivia S.; Wilson, Michael D.; Ellis, James

doi:10.1101/2023.03.01.530249

Cited by 3 publications

(2 citation statements)

References 62 publications

(105 reference statements)

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“…The longer 3'UTRs, the more cis-regulatory elements residing and more stable gene expression [38][39][40] . We found that the high-redundant targets have the longest 3'UTRs (peaking at 1,024 ~ 2,048 bp), followed by the low-redundant (peaking at 256 ~ 512 bp), non-redundant (peaking at 128 ~ 256 bp) and non-motif targets (peaking at 128 ~ 256 bp; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness

Liufu,

Dai,

Lan

et al. 2024

Preprint

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MicroRNAs (miRNAs) act as trans-acting elements and form composite feedforward circuits (cFFCs) in conjunction with transcription factors (TFs), leading to redundancy in network motifs and influencing gene expression regulation. However, the maintenance of miRNA-mediated regulatory redundancy and its impact on gene expression evolution remain elusive. Using public ChIP-seq/ChIP-chip and ATAC-seq data, we constructed miRNA-mediated cFFCs in Drosophila melanogaster embryos and found that most of predicted miRNA targets are involved in redundant cFFCs. Population genetics analysis revealed that highly redundant cFFCs are subjected to stronger purifying selection than low-redundant or non-redundant cFFCs. This redundancy negatively correlates with expression divergence between D. melanogaster and D. simulans, and is associate with expression stability in D. melanogaster embryos under heat shock. Moreover, highly redundant cFFCs mainly target older genes or young genes with broader expression. Our findings emphasize the biological significance of miRNA-mediated cFFC redundancy in mediating the robustness of gene expression during evolution.

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Section: Resultsmentioning

confidence: 99%

MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness

Liufu,

Dai,

Lan

et al. 2024

Preprint

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show abstract

“…The rates of RNA synthesis and degradation can be kinetically coupled by establishing a feedback loop between RNA synthesis in the nucleus to degradation of their corresponding RNAs in the cytoplasm ( 62 – 69 ). This mechanism has been well established in yeast and recently demonstrated in human cells ( 70 , 71 ); however, all the studies were done in a steady-state condition and its regulatory mechanisms, particularly under a dynamic condition, remain elusive (reviewed in ref. 63 ).…”

Section: Discussionmentioning

confidence: 99%

Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts

Unruh,

Weidemann,

Miao

et al. 2024

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

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Circadian RNA expression is essential to ultimately regulate a plethora of downstream rhythmic biochemical, physiological, and behavioral processes. Both transcriptional and posttranscriptional mechanisms are considered important to drive rhythmic RNA expression; however, the extent to which each regulatory process contributes to the rhythmic RNA expression remains controversial. To systematically address this, we monitored RNA dynamics using metabolic RNA labeling technology during a circadian cycle in mouse fibroblasts. We find that rhythmic RNA synthesis is the primary contributor of 24-h RNA rhythms, while rhythmic degradation is more important for 12-h RNA rhythms. These rhythms were predominantly regulated by Bmal1 and/or the core clock mechanism, and the interplay between rhythmic synthesis and degradation has a significant impact in shaping rhythmic RNA expression patterns. Interestingly, core clock RNAs are regulated by multiple rhythmic processes and have the highest amplitude of synthesis and degradation, presumably critical to sustain robust rhythmicity of cell-autonomous circadian rhythms. Our study yields invaluable insights into the temporal dynamics of both 24- and 12-h RNA rhythms in mouse fibroblasts.

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Coordination of rhythmic RNA synthesis and degradation orchestrates 24-hour and 12-hour RNA expression patterns in mouse fibroblasts

Unruh¹,

Weidemann²,

Kojima³

2023

Preprint

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Circadian RNA expression is essential to ultimately regulate a plethora of downstream rhythmic biochemical, physiological, and behavioral processes. Both transcriptional and post-transcriptional mechanisms are considered important to drive rhythmic RNA expression, however, the extent to which each regulatory process contributes to the rhythmic RNA expression remains controversial. To systematically address this, we monitored RNA dynamics using metabolic RNA labeling technology during a circadian cycle in mouse fibroblasts. We find that rhythmic RNA synthesis is the primary contributor of 24 hr RNA rhythms, while rhythmic degradation is more important for 12 hr RNA rhythms. These rhythms were predominantly regulated by Bmal1 and/or the core clock mechanism, and interplay between rhythmic synthesis and degradation has a significant impact in shaping rhythmic RNA expression patterns. Interestingly, core clock RNAs are regulated by multiple rhythmic processes and have the highest amplitude of synthesis and degradation, presumably critical to sustain robust rhythmicity of cell-autonomous circadian rhythms. Our study yields invaluable insights into the temporal dynamics of both 24 hr and 12 hr RNA rhythms in mouse fibroblasts.

show abstract

Transcriptional buffering and 3ʹUTR lengthening are shaped during human neurodevelopment by shifts in mRNA stability and microRNA load

Cited by 3 publications

References 62 publications

MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness

MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness

Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts

Coordination of rhythmic RNA synthesis and degradation orchestrates 24-hour and 12-hour RNA expression patterns in mouse fibroblasts

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