ABSTRACT
Ribosomal RNAs are processed in a complex pathway. We profiled rRNA processing intermediates in yeast at single-molecule and single-nucleotide levels with circularization, targeted amplification and deep sequencing (CircTA-seq), gaining significant mechanistic insights into rRNA processing and surveillance. The long form of the 5' end of 5.8S rRNA is converted to the short form and represents an intermediate of a unified processing pathway. The initial 3' end processing of 5.8S rRNA involves trimming by Rex1 and Rex2 and Trf4-mediated polyadenylation. The 3' end of 25S rRNA is formed by sequential digestion by four Rex proteins. Intermediates with an extended A1 site are generated during 5' degradation of aberrant 18S rRNA precursors. We determined precise polyadenylation profiles for pre-rRNAs and show that the degradation efficiency of polyadenylated 20S pre-rRNA critically depends on poly(A) lengths and degradation intermediates released from the exosome are often extensively re-polyadenylated.
ABSTRACT
Overexpression of the MYC oncogene is a molecular hallmark of both cancer initiation and progression. Targeting MYC is a logical and effective cancer therapeutic strategy. A special DNA secondary structure, the G-quadruplex (G4), is formed within the nuclease hypersensitivity element III1 (NHE III1) region, located upstream of the MYC gene's P1 promoter that drives the majority of its transcription. Targeting such G4 structures has been a focus of anticancer therapies in recent decades. Thus, a comprehensive review of the MYC G4 structure and its role as a potential therapeutic target is timely. In this review, we first outline the discovery of the MYC G4 structure and evidence of its formation in vitro and in cells. Then, we describe the functional role of G4 in regulating MYC gene expression. We also summarize three types of MYC G4-interacting proteins that can promote, stabilize and unwind G4 structures. Finally, we discuss G4-binding molecules and the anticancer activities of G4-stabilizing ligands, including small molecular compounds and peptides, and assess their potential as novel anticancer therapeutics.
