ABSTRACT
GEMIN5 is essential for core assembly of small nuclear Ribonucleoproteins (snRNPs), the building blocks of spliceosome formation. Loss-of-function mutations in GEMIN5 lead to a neurodevelopmental syndrome among patients presenting with developmental delay, motor dysfunction, and cerebellar atrophy by perturbing SMN complex protein expression and assembly. Currently, molecular determinants of GEMIN5-mediated disease have yet to be explored. Here, we identified SMN as a genetic suppressor of GEMIN5-mediated neurodegeneration in vivo. We discovered that an increase in SMN expression by either SMN gene therapy replacement or the antisense oligonucleotide (ASO), Nusinersen, significantly upregulated the endogenous levels of GEMIN5 in mammalian cells and mutant GEMIN5-derived iPSC neurons. Further, we identified a strong functional association between the expression patterns of SMN and GEMIN5 in patient Spinal Muscular Atrophy (SMA)-derived motor neurons harboring loss-of-function mutations in the SMN gene. Interestingly, SMN binds to the C-terminus of GEMIN5 and requires the Tudor domain for GEMIN5 binding and expression regulation. Finally, we show that SMN upregulation ameliorates defective snRNP biogenesis and alternative splicing defects caused by loss of GEMIN5 in iPSC neurons and in vivo. Collectively, these studies indicate that SMN acts as a regulator of GEMIN5 expression and neuropathologies.
Subject(s)
Muscular Atrophy, Spinal , RNA-Binding Proteins , Humans , Motor Neurons/metabolism , Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/metabolism , Ribonucleoproteins, Small Nuclear/genetics , Ribonucleoproteins, Small Nuclear/chemistry , Ribonucleoproteins, Small Nuclear/metabolism , RNA-Binding Proteins/metabolism , SMN Complex Proteins/genetics , Tudor DomainABSTRACT
The present study aimed at the development of a groundnut-based dehydrated paneer type product which could serve as an instant vegan protein source. In the process of preparing groundnut paneer, a ratio of 1:5 of groundnut to water and 2.0% calcium chloride (CaCl2) solution was used for the preparation of groundnut paneer and the product was evaluated for physicochemical, instrumental color, instrumental textural, and sensory characteristics. The developed paneer cubes (1.5 × 1.5 × 1 cm) were dehydrated using a vacuum-assisted microwave dryer at different microwave powers (200-600 W, 250 mbar vacuum). The minimum bulk density (0.55 g/cc) and maximum rehydration ratio (2.9) were recorded in the sample dehydrated at 600 W. The samples dried at 600 W also showed significantly (p < .05) higher L* values, softer texture and high sensory scores for color, aroma, taste, texture, and overall acceptability after rehydration.
