Cappelli, S. | bioRxiv Science

bioRxiv2023

Axon guidance genes are regulated by TDP-43 and RGNEF through the rate of long-intron processing.

Rho guanine nucleotide exchange factor (RGNEF) is a guanine nucleotide exchange factor (GEF) mainly involved in regulating the activity of Rho-family GTPases. Previous work has shown that RGNEF inclusions in the spinal motor neurons of ALS patients co-localise with TDP-43, the major RNA binding protein aggregating in the brain and spinal cord of ALS patients. To further characterise their relationship, we have compared the transcriptomic profiles of neuronal-like cells depleted of TDP-43 and RGNEF and show that these two factors predominantly act in an antagonistic manner when regulating the expression of axon guidance genes. From a mechanistic point of view, our experiments show that the effect of these factors on the processivity of long introns can explain their mode of action. Our findings highlight that neurodegenerative processes at the RNA level can often represent the result of combinatorial interactions between different RNA binding factors, leading to a better understanding of pathogenic mechanisms occurring in patients where more than one specific protein may be aggregating in their neurons.

neuroscience↗

bioRxiv2019

Decomposition disentangled: a test of the multiple mechanisms by which nitrogen enrichment alters litter decomposition

O_LINitrogen (N) enrichment has direct effects on ecosystem functioning by altering soil abiotic conditions and indirect effects by reducing plant diversity and shifting plant functional composition from dominance by slow to fast growing species. Litter decomposition is a key ecosystem function and is affected by N enrichment either by a change in litter quality (the recalcitrance of the plant material) or through a change in soil quality (the abiotic and biotic components of the soil that affect decomposition). The relative importance of soil and litter quality and how the direct and effects of N alter them remains poorly known.\nC_LIO_LIWe designed a large grassland field experiment manipulating N enrichment, plant species richness and functional composition in a full factorial design. We used three complementary litter bag experiments and a novel structural equation modelling approach to quantify the relative effects of the treatments on litter and soil quality and their importance for total decomposition.\nC_LIO_LIOur results indicate that total decomposition was mostly driven by changes in litter quality rather than soil quality. Litter quality was affected by the nutrient contents (N and calcium) and structural components of the litter (leaf dry matter content, fibres). N enrichment increased litter decomposition mostly indirectly through a shift in functional composition toward faster growing plant species producing higher quality litter. N enrichment also had effects on soil, by directly and indirectly affected vegetation cover, but this had relatively few consequences for the total decomposition rate.\nC_LIO_LISynthesis. Our approach provides a mechanistic tool to test the drivers of litter decomposition across different ecosystems. Our results show that functional composition is more important than richness or soil quality in determining litter decomposition and that N enrichment effects mainly occur via above- rather than belowground processes. This highlights the importance of considering shifts in plant species composition when assessing the effects of N enrichment on decomposition.\nC_LI

ecology↗