bims-ciryme 2023-01-01 papers

on Circadian rhythms and metabolism

Issue of 2023–01–01
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham

A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules.
Nuclear-cytoplasmic compartmentalization of cyclin B1-Cdk1 promotes robust timing of mitotic events.

Cell Rep. 2022 Dec 27. pii: S2211-1247(22)01775-2. [Epub ahead of print]41(13): 111879

A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules.

Kathrina D Castillo, Cheng Wu, Zhaolan Ding, Osiris K Lopez-Garcia, Emma Rowlinson, Matthew S Sachs, Deborah Bell-Pedersen.

  Phosphorylation of Neurospora crassa eukaryotic initiation factor 2 α (eIF2α), a conserved translation initiation factor, is clock controlled. To determine the impact of rhythmic eIF2α phosphorylation on translation, we performed temporal ribosome profiling and RNA sequencing (RNA-seq) in wild-type (WT), clock mutant Δfrq, eIF2α kinase mutant Δcpc-3, and constitutively active cpc-3c cells. About 14% of mRNAs are rhythmically translated in WT cells, and translation rhythms for ∼30% of these mRNAs, which we named circadian translation-initiation-controlled genes (cTICs), are dependent on the clock and CPC-3. Most cTICs are expressed from arrhythmic mRNAs and contain a P-body (PB) localization motif in their 5' leader sequence. Deletion of SNR-1, a component of cytoplasmic messenger ribonucleoprotein granules (cmRNPgs) that include PBs and stress granules (SGs), and the PB motif on one of the cTIC mRNAs, zip-1, significantly alters zip-1 rhythmic translation. These results reveal that the clock regulates rhythmic translation of specific mRNAs through rhythmic eIF2α activity and cmRNPg metabolism.

Keywords:  CP: Molecular biology; CPC-3; GCN2; Neurospora crassa; P-body; circadian clock; cytoplasmic messenger ribonucleoprotein granules; eIF2α; ribosome profiling; translation control

DOI:  https://doi.org/10.1016/j.celrep.2022.111879
Cell Rep. 2022 Dec 27. pii: S2211-1247(22)01766-1. [Epub ahead of print]41(13): 111870

Nuclear-cytoplasmic compartmentalization of cyclin B1-Cdk1 promotes robust timing of mitotic events.

Gembu Maryu, Qiong Yang.

  The cyclin-dependent kinase (Cdk1) oscillator is widely characterized in homogenized cytosolic extracts, leaving unclear the impact of nucleocytoplasmic compartmentalization. Here, by developing a Förster resonance energy transfer (FRET) biosensor, we track Cdk1 spatiotemporal dynamics in reconstituted cells with or without side by side and find compartmentalization significantly modulates clock properties previously found in bulk studies. Although nucleus-absent cells display highly tunable frequency, the nucleus-present cells maintain constant frequency against cyclin B1 variations. Despite high expression variability, cyclin degraded within the same duration, enabling a robust mitotic phase. Moreover, Cdk1 and cyclin B1 cycle rigorously out-of-phase, ensuring wide phase-plane orbits, essential for oscillation robustness. Although Cdk1 in homogeneous extracts is well known for delayed switch-like activation, we find active cyclin B1-Cdk1 accumulates in nuclei, without delay, until the nuclear envelope breakdown (NEB) when another abrupt activation triggers anaphase. Cdk1 biphasic activation and spatial compartmentalization may together coordinate the accurate ordering of different downstream events.

Keywords:  CP: Cell biology; FRET imaging; cell cycle robustness; cell-free extracts; cyclin-dependent kinase (Cdk); droplet microfluidics; frequency tunability; limit-cycle oscillations; nuclear-cytoplasmic compartmentalization; phase-plane trajectory; synthetic cells

DOI:  https://doi.org/10.1016/j.celrep.2022.111870