An expanded hexanucleotide repeat in C9orf72 causes amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor, Spt4, selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Knockdown of SUPT4H1, the human Spt4 ortholog, similarly decreased production of sense and antisense RNA foci as well as DPR proteins in patient cells. Therapeutic targeting of a single factor to eliminate c9FTD/ALS pathological features offers advantages over approaches that require targeting sense and antisense repeats separately.

The multifunctional ribonuclease RNase E and the 3-exonuclease polynucleotide phosphorylase (PNPase) are major components of an Escherichia coli ribonucleolytic "machine" that has been termed the RNA degradosome. Previous work has shown that poly(A) additions to the 3 ends of RNA substrates affect RNA degradation by both of these enzymes. To better understand the mechanism(s) by which poly(A) tails can modulate ribonuclease action, we used selective binding in 1 M salt to identify E. coli proteins that interact at high affinity with poly(A) tracts. We report here that CspE, a member of a family of RNA-binding "cold shock" proteins, and S1, an essential component of the 30 S ribosomal subunit, are poly(A)-binding proteins that interact functionally and physically, respectively, with degradosome ribonucleases. We show that purified CspE impedes poly(A)-mediated 3 to 5 exonucleolytic decay by PNPase by interfering with its digestion through the poly(A) tail and also inhibits both internal cleavage and poly(A) tail removal by RNase E. The ribosomal protein S1, which is known to interact with sequences at the 5 ends of mRNA molecules during the initiation of translation, can bind to both RNase E and PNPase, but in contrast to CspE, did not affect the ribonucleolytic actions of these enzymes. Our findings raise the prospect that E. coli proteins that bind to poly(A) tails may link the functions of degradosomes and ribosomes.

Dryland ecosystems cover more than 30% of the terrestrial area of China, while processes that shape the biogeographic patterns of bacterial and fungal β-diversity have rarely been evaluated synchronously. To compare the biogeographic patterns and its drivers of bacterial and fungal β-diversity, we collected 62 soil samples from a typical dryland region of northwest China. We assessed bacterial and fungal communities by sequencing bacterial 16S rRNA gene and fungal ITS data. Meanwhile, the β-diversity was decomposed into two components: species replacement (species turnover) and nestedness to further explore the bacterial and fungal β-diversity patterns and its causes. The results show that both bacterial and fungal β-diversity were derived almost entirely from species turnover rather than from species nestedness. Distance-decay relationships confirmed that the geographic patterns of bacterial and fungal β-diversity were significantly different. Environmental factors had the dominant influence on both the bacterial and fungal β-diversity and species turnover, however, the role of geographic distance varied across bacterial and fungal communities. Furthermore, both bacterial and fungal nestedness did not significantly respond to the environmental and geographic distance. Our findings suggest that the different response of bacterial and fungal species turnover to dispersal limitation and other, unknown processes may result in different biogeographic patterns of bacterial and fungal β-diversity in the drylands of northwest China. Together, we highlight that the drivers of β-diversity patterns vary between bacterial and fungal communities, and microbial β-diversity are driven by multiple factors in the drylands of northwest China.

Zeins, the predominent storage proteins in maize endosperm, are encoded by multiple genes and gene families. However, only a few transcriptional factors for zein gene regulation have been functionally characterized. In this study, a MADS-box protein, namely ZmMADS47, was identified as an Opaque2 (O2) interacting protein via yeast two-hybrid screening. The N-terminal portion of ZmMADS47 contains a nuclear localization signal (NLS), and its C-terminal portion contains a transcriptional activation domain (AD). Interestingly, the transcriptional activation activity is blocked in its full length form, suggesting conformational regulation of the AD. Molecular and RNA-seq analyses of ZmMADS47 RNAi lines revealed down regulation of α-zein and 50-kD γ-zein genes. ZmMADS47 binds the CATGT motif in promoters of these zein genes, but ZmMADS47 alone is not able to transactivate the promoters. However, when both O2 and ZmMADS47 are present, the transactivation of these promoters was greatly enhanced. This enhancement was dependent on the AD function of ZmMADS47 and the interaction between ZmMADS47 and O2, but it was independent from the AD function of O2. Therefore, it appears interaction with O2 activates ZmMADS47 on zein gene promoters.