Intronic RNA secondary structural information captured for the human pre-mRNA.

To address the lack of intronic reads in secondary structure probing data for the human pre-mRNA, we developed a method that combines spliceosomal inhibition with RNA probing and sequencing. Here, the SIRP-seq method was applied to study the secondary structure of human RNAs by chemically probing HeLa cells with dimethyl sulfate in the presence of the small molecule spliceosome inhibitor pladienolide B. Pladienolide B binds to the SF3B complex of the spliceosome to inhibit intron removal during splicing, resulting in retained intronic sequences.

Structural Context of a Critical Exon of Spinal Muscular Atrophy Gene.

Humans contain two nearly identical copies of genes, and . Deletion or mutation of causes spinal muscular atrophy (SMA), one of the leading genetic diseases associated with infant mortality. is unable to compensate for the loss of due to predominant exon 7 skipping, leading to the production of a truncated protein.

microRNA-mediated regulation of microRNA machinery controls cell fate decisions.

microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRISC, are regulated during development is still limited. We previously showed that repressing the production of one Argonaute protein, Ago2, by Trim71 is important for mouse embryonic stem cells (mESCs) self-renewal (Liu et al.