No abstract

Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes. Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3' end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3' fragment of U6 snRNA, at 2.8 Å resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3-2-8-4-7-5-6. The four uridine nucleotides at the 3' end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3' end is sandwiched by His 36 and Arg 69 from Lsm3, through π-π and cation-π interactions, respectively. The distinctive end-recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing.

An inverted perovskite solar cell bilaterally passivated by polystyrene exhibits an efficiency of 19.99% with a high VOC of 1.149 V.

The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOPP94R, EZH1Q571R and ZNF148 mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin.

Background The results of previous studies on the usefulness of free triiodothyronine (FT3) to free thyroxine (FT4) are controversial. We investigated the usefulness of FT3, FT4, and FT3/FT4 ratio in differentiating Graves' disease (GD) from destructive thyroiditis. Methods A total of 126 patients with untreated GD, 36 with painless thyroiditis, 18 with painful subacute thyroiditis, and 63 healthy controls, were recruited. The levels of FT3 and FT4 and the FT3/FT4 ratios for the different etiologies of thyrotoxicosis were evaluated separately by receiver operating characteristic (ROC) curve analysis. The expression levels of type 1 and type 2 deiodinase (DIO1 and DIO2) in thyroid tissues were also investigated. Results The optimal cut-off values were 7.215 pmol/L for FT3, 21.71 pmol/L for FT4, and 0.4056 for the FT3/FT4 ratio. The specificity and positive predictive value of the FT3/FT4 ratio were highest for values > 0.4056. DIO1 mRNA expression was significantly higher in the thyroid tissue of patients with GD (P = 0.013). Conclusions We demonstrated that the FT3/FT4 ratio was useful in differentiating GD from destructive thyroiditis. In addition, a relatively high expression of type 1 deiodinase in the thyroid might be responsible for the high FT3/FT4 ratio in patients with GD.