Distinct Hormone Signalling-Modulation Activities Characterize Two Maize Endosperm-Specific Type-A Response Regulators

ZmTCRR1 and 2 are type-A response regulators expressed in the maize endosperm transfer cells (TC). While type-B response regulators transcriptionally control canonical type-A response regulators, as part of the cytokinin signal transduction mechanism, the ZmTCRRs are regulated by ZmMRP1, a master regulator of TC identity. In addition, the corresponding proteins are not detected in the TC, accumulating in the inner endosperm cells instead. These features suggest these molecules are not involved in classical, cell-autonomous, cytokinin signalling pathways. Using transgenic Arabidopsis plants ectopically expressing these genes, we have shown that ZmTCRR1 and 2 can modulate auxin and cytokinin signalling, respectively. In Arabidopsis, the ectopic expression of ZmTCRR2 blocked, almost completely, cytokinin perception. Given the conservation of these signalling pathways at the molecular level, our results suggest that the ZmTCRRs modulate cytokinin and auxin perception in the inner endosperm cells.Ministerio de Economía y Competitividad-MINECOAgencia Estatal de Investigación-AE

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m(7)G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m(7)G tRNA methylation in cancer cell translation control and tumour biology