The levels of the long non-coding RNA MALAT1 affect cell viability and modulate TDP-43 binding to mRNA in the nucleus.

TAR DNA-binding protein (TDP-43) and Metastasis Associated Lung Adenocarcinoma Transcript (MALAT1) RNA are both abundantly expressed in the human cell nucleus. Increased interaction of TDP-43 and MALAT1, as well as dysregulation of TDP-43 function, was previously identified in brain samples from patients with neurodegenerative disease compared to healthy brain tissues. We hypothesized that TDP-43 function may depend in part on MALAT1 expression levels.

Dissection of protein and RNA regions required for SPEN binding to XIST A-repeat RNA.

XIST noncoding RNA promotes the initiation of X chromosome silencing by recruiting the protein SPEN to one X chromosome in female mammals. The SPEN protein is also called SHARP (SMRT and HDAC-associated repressor protein) and MINT (Msx-2 interacting nuclear target) in humans. SPEN recruits N-CoR2 and HDAC3 to initiate histone deacetylation on the X chromosome, leading to the formation of repressive chromatin marks and silencing gene expression.

High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch.

Riboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions.