Transcription directionality is licensed by Integrator at active human promoters.

A universal characteristic of eukaryotic transcription is that the promoter recruits RNA polymerase II (RNAPII) to produce both precursor mRNAs (pre-mRNAs) and short unstable promoter upstream transcripts (PROMPTs) toward the opposite direction. However, how the transcription machinery selects the correct direction to produce pre-mRNAs is largely unknown. Here, through multiple acute auxin-inducible degradation systems, we show that rapid depletion of an RNAPII-binding protein complex, Integrator, results in robust PROMPT accumulation throughout the genome. Interestingly, the accumulation of PROMPTs is compensated by the reduction of pre-mRNA transcripts in actively transcribed genes. Consistently, Integrator depletion alters the distribution of polymerase between the sense and antisense directions, which is marked by increased RNAPII-carboxy-terminal domain Tyr1 phosphorylation at PROMPT regions and a reduced Ser2 phosphorylation level at transcription start sites. Mechanistically, the endonuclease activity of Integrator is critical to suppress PROMPT production. Furthermore, our data indicate that the presence of U1 binding sites on nascent transcripts could counteract the cleavage activity of Integrator. In this process, the absence of robust U1 signal at most PROMPTs allows Integrator to suppress the antisense transcription and shift the transcriptional balance in favor of the sense direction.

Ribosomal frameshifting at normal codon repeats recodes functional chimeric proteins in human.

Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans-frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans-frame proteins for viral replication or regulation of other biological processes. In humans, however, functional trans-frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assays, we show that short codon repeats could act as cis-acting elements that stimulate ribosomal frameshifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans-frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans-frame protein (HDAC1-FS) functions by antagonizing the activities of HDAC1, thus affecting cell migration and apoptosis. These data suggest a novel type of translational recoding associated with codon repeats, which may expand the coding capacity of mRNA and diversify the regulation in human.

Impact of acceleration of agricultural and industrial waste conditioning on thermal drying of sewage sludge.

Improving the dewatering performance of sludge is a necessary advancement for collaborative sludge disposal and energy-efficient utilization in power plants. Herein, the effects of temperature changes and the addition of drying accelerators derived from agricultural and industrial waste on the drying characteristics of sewage sludge (SS) were investigated from the perspectives of drying kinetics and micromorphology. According to the results, the drying time for sludge significantly showed a clear downward trend via medium-low temperature (160 °C) thermal drying, which subsequently reduced the energy input substantially. When the drying temperature was 160 °C, the ideal addition proportions of rice husk (RH), sludge ash (SA), and coal ash (CA) comprised 15%. The addition of SA prominently boosted the drying rate constant of the original sludge by 48%. Additionally, SEM images along with the spectral dimension obtained via fractal theory explicitly clearly demonstrated that SS + SA had more loose pore channels than other mixed samples. This provided a convenient approach to ensure the evaporation and migration of moisture and thereby shorten the drying time effectively. Consequently, the addition of sludge ash as a drying accelerator can promote the deep dewatering of sludge.