Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

G-quadruplex Structure in miRNA / 中国生物化学与分子生物学报

G-quadruplex (G4) is a non-canonical nucleic acid secondary structure composed of guanine-rich DNA or RNA sequences. In the past few decades, researchers have focused on the G-rich sequences in gene promoter region, UTR, telomere and other common gene functional regions, to understand the relationship between their structure and function. In recent years, due to the in-depth study of non-coding RNA in diseases, G-rich sequences in non-coding RNA, especially miRNA, have attracted more attention. G-rich sequence has been involved in all physiological processes of miRNA synthesis, from primary miRNA (pri-miRNA), precursor miRNA (pre-miRNA) to mature miRNA: the dynamic balance formed between the G-quadruplex and the RNA stem-loop structure affects the maturation process of primary and precursor miRNA, causing the change of mature miRNA and the complementary pairing between miRNA and mRNA. This review focused on the dynamic changes between G4 and hairpin structure, and expounded the role of G-rich sequence in pri-miRNA, pre-miRNA, mature miRNA and mRNA. The important role of G-quadruplex in the maturation and function of miRNA was also discussed. It was concluded that the changes of external regulatory factors such as ionic conditions (K+, Mg +, K+ + Mg, Li +Mg +, etc) and G-quadruplex ligand molecules (destabilizer TMPyP4, etc) could regulate the balance between G-quadruplex and stem-loop structure, thus modulating the functions of miRNA. This review may help providing ideas and directions for the study of G-quadruplex function and regulation.