Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N6-methyladenosine (m6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m6A motifs are enriched in circRNAs and a single m6A site is sufficient to drive translation initiation. This m6A-driven translation requires initiation factor eIF4G2 and m6A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m6A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.

Key Points 13• High-frequency flow variations enhance hyporheic exchange and create long-term alterations 14 to thermal regimes and biogeochemical reactions. 15• High-frequency flow variations have the largest impact on thermal regimes and 16 biogeochemical reactions in hyporheic zone under drought. 17• Spatial distribution of biogeochemical hot spots depends more on the subsurface hydraulic 18 properties than high-frequency flow variations.

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We tested whether the reduction of metabolic rate (MR) in hibernating Cercartetus nanus (Marsupialia, 36 g) is better explained by the reduction of body temperature (Tb), the differential (ΔT) between Tb and air temperature (Ta), or thermal conductance (C). Above the critical Ta during torpor (Ttc) of 4.8 ± 0.7°C, where the Tb was not regulated, the steady-state MR was an exponential function of Tb( r 2 = 0.92), and the overall Q10 was 3.3. However, larger Q10 values were observed at high Tb values during torpor, particularly within the thermoneutral zone (Q10 = 9.5), whereas low Q10 values were observed below Tb 20°C (Q10 = 1.9). The ΔT did not change over Ta 5–20°C, although MR fell, and therefore the two variables were not correlated. Below the Ttc, Tb was regulated at 6.1 ± 1.0°C and MR increased proportionally to ΔT. Our study suggests that MR in torpid C. nanus is largely determined by temperature effects and metabolic inhibition. In contrast, ΔT explains MR only below the Ttc and C appears to affect MR only indirectly via changes of Tb, suggesting that ΔT and C play only a secondary role in MR reduction during hibernation.

In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community's traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators.

Unconventional resources such as shale gas and tight oil are contributing more and more significantly in the energy nexus. However, porosity and permeability of these reservoirs are extremely low; therefore, stimulating technologies are required. The state-of-the-art solution for such a target is water fracturing, but its application suffers from massive water usage and related environmental issues. As a greener alternative, fracturing with CO 2 may bring multiple benefits, including effective fracturing, enhanced recovery, carbon storage, and others.