Furthermore, Drosha has been recently shown to promote alternative splicing of exon 5 of eIF4H gene in cleavage-independent manner (Havens et al., 2014).
Consequently, this result provides a molecular explanation for the ability of Drosha to regulate gene expression in a miRNA- and cleavage-independent manner.
Taken together, these results suggest a model whereby Drosha promotes gene expression in a cleavage-independent manner by binding to RNA hairpins formed at the 5′ ends of the nascent RNAs and interacting with CBP80 and Pol II, through its N-terminal RS domain.
Our results suggest that the MRE β-loop stabilises the extended conformation of a substrate by directly binding to it through β-strand addition, thus promoting substrate cleavage in a manner similar to the edge strand.
Initial studies showed that a sequence comprised of a region of 18 amino acid residues from 2A followed by a proline from protein 2B are enough to promote cleavage in a cotranslational manner.
The mechanism of action supports the cell death through apoptosis in a caspase-independent manner without cleavage of poly (ADP-ribose) polymerase (PARP), even though the compounds cause plasma membrane morphological changes.
In this manner, the cleavage of ubiquitin by elaD could just be an artificial byproduct of our assays, while the true substrate is of bacterial origin.
Both, Amyloid precursor like protein-1 (andP1) Amyloidloid precursor like protein-2 (areP2) are substrates of α-, γ-, and ε-secretase cleavage in a similar manner as APP, while APLP2 can also be cleaved by β-secretase [67].
Previously, it was reported that NMDAR stimulation in cortical neurons promotes, in a Ca2+-dependent manner, p35 cleavage to p25 by calpain leading to Cdk5 activation.
Accordingly, manipulating substrate and gate dynamics in living cells shifted cleavage sites in a manner incompatible with extended sequence binding, but correlated with a membrane-and-helix-exit propensity scale.
