Chromatin-associated circRNA ciCRLF3(2) regulates cell differentiation blockage via activating non-homologous end joining-based DNA repair.

DNA damage response (DDR) is a complicated network that responds to DNA lesions to prevent their accumulation; a defective DDR is one hallmark of cancer. Although targeting DDR pathways has been considered as a therapeutic approach, DDR inhibitors have also been reported ineffective for treating some low mutation burden cancers, such as Mixed-lineage leukemia (MLL)-rearranged (MLL-r) leukemia, a clinically fatal and refractory malignancy. Exploring the roles and mechanisms of DDR pathways in these low mutation burden cancers may help understand the chromatin biology and develop therapeutic strategies.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

Background: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements.

New insight into circRNAs: characterization, strategies, and biomedical applications.

Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism.

METTL3 protects METTL14 from STUB1-mediated degradation to maintain m A homeostasis.

N -Methyladenosine (m A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m A homeostasis remain elusive.

The snoRNA-like lncRNA LNC-SNO49AB drives leukemia by activating the RNA-editing enzyme ADAR1.

Long noncoding RNAs (lncRNAs) are usually 5' capped and 3' polyadenylated, similar to most typical mRNAs. However, recent studies revealed a type of snoRNA-related lncRNA with unique structures, leading to questions on how they are processed and how they work. Here, we identify a novel snoRNA-related lncRNA named LNC-SNO49AB containing two C/D box snoRNA sequences, SNORD49A and SNORD49B; and show that LNC-SNO49AB represents an unreported type of lncRNA with a 5'-end m7G and a 3'-end snoRNA structure.