PLX090443

GSE129590: Studying the selectivity of a small molecule Synucleozid on transcriptome

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

One strategy to drugging undruggable proteins is to directly target the mRNA that encodes them, thereby inhibit translation and reducing protein levels. Inforna, a sequence-based design approach to target RNA, enables the design of a small molecule Synucleozid that binds SNCA mRNA which encodes alpha-synuclein. Herein, we investigate the selectivity of Synucleozid on the whole transcriptome. Based on mechanistic studies, Synucleozid targets IRE locates in 5' UTR of SNCA mRNA and reduces alpha-synuclein protein levels by decreasing the amount of SNCA mRNA loaded into polysomes. Different from alpha-synuclein siRNA, Synucleozid binds mRNA and affect its function without regulating mRNA expression. SOURCE: Peiyuan Zhang (doctorpeterzhang@gmail.com) - TSRI