Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells.

U7 snRNA is part of the U7 snRNP complex, required for the 3' end processing of replication-dependent histone pre-mRNAs in S phase of the cell cycle. Here, we show that U7 snRNA plays another function in inhibiting the expression of a subset of long terminal repeats of human endogenous retroviruses (HERV1/LTR12s) and LTR12-containing long intergenic noncoding RNAs (lincRNAs), both bearing sequence motifs that perfectly match the 5' end of U7 snRNA. We demonstrate that U7 snRNA inhibits LTR12 and lincRNA transcription and propose a mechanism in which U7 snRNA hampers the binding/activity of the NF-Y transcription factor to CCAAT motifs within LTR12 elements.

Modulatory role of RNA helicases in MBNL-dependent alternative splicing regulation.

Muscleblind-like splicing regulators (MBNLs) activate or repress the inclusion of alternative splicing (AS) events, enabling the developmental transition of fetal mRNA splicing isoforms to their adult forms. Herein, we sought to elaborate the mechanism by which MBNLs mediate AS related to biological processes. We evaluated the functional role of DEAD-box (DDX) RNA helicases, DDX5 and DDX17 in MBNL-dependent AS regulation.

Imprinted small nucleolar RNAs: Missing link in development and disease?

The 14q32.2 (DLK1-DIO3) and 15q11-q13 (SNURF-SNRPN) imprinted gene loci harbor the largest known small nucleolar RNA clusters expressed from the respective maternal and paternal alleles. Recent studies have demonstrated significant roles for the 15q11-q13 located SNORD115-SNORD116 C/D box snoRNAs in Prader-Willi syndrome (PWS), a neurodevelopmental disorder.

FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications.

FUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this work, we show that FUS depletion results in the differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2'-O methylation (2'-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2'-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells.

Role of Long Intergenic Noncoding RNAs in Cancers with an Overview of MicroRNA Binding.

Long intergenic noncoding RNAs are transcripts originating from the regions without annotated coding genes. They are located mainly in the nucleus and regulate gene expression. Long intergenic noncoding RNAs can be also found in the cytoplasm acting as molecular sponges of certain microRNAs.

The Novel Role of hnRNP UL1 in Human Cell Nucleoli.

hnRNP UL1 plays an important role in cell nuclei, where it is recruited to DNA damage sites and is involved in the repair of DNA double-strand breaks. Furthermore, this protein is known as a transcriptional repressor of RNA polymerase II genes. In the present study, we have shown that hnRNP UL1 is also localized in the nucleoli of human cells.

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders.

Long intergenic noncoding RNAs (lincRNAs) are a class of independently transcribed molecules longer than 200 nucleotides that do not overlap known protein-coding genes. LincRNAs have diverse roles in gene expression and participate in a spectrum of biological processes. Dysregulation of lincRNA expression can abrogate cellular homeostasis, cell differentiation, and development and can also deregulate the immune and nervous systems.

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs.

In recent functional genomics studies, a large number of non-coding RNAs have been identified. It has become increasingly apparent that noncoding RNAs are crucial players in a wide range of cellular and physiological functions. They have been shown to modulate gene expression on different levels, including transcription, post-transcriptional processing, and translation.

ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells.

Genes encoding replication-dependent histones lack introns, and the mRNAs produced are a unique class of RNA polymerase II transcripts in eukaryotic cells that do not end in a polyadenylated tail. Mature mRNAs are thus formed by a single endonucleolytic cleavage that releases the pre-mRNA from the DNA and is the only processing event necessary. U7 snRNP is one of the key factors that determines the cleavage site within the 3'UTR of replication-dependent histone pre-mRNAs.

U7 snRNA: A tool for gene therapy.

Most U-rich small nuclear ribonucleoproteins (snRNPs) are complexes that mediate the splicing of pre-mRNAs. U7 snRNP is an exception in that it is not involved in splicing but is a key factor in the unique 3' end processing of replication-dependent histone mRNAs. However, by introducing controlled changes in the U7 snRNA histone binding sequence and in the Sm motif, it can be used as an effective tool for gene therapy.

Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.

Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins.

Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression.

Background: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3' end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression.

FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors.

Replication-dependent histone genes are up-regulated during the G1/S phase transition to meet the requirement for histones to package the newly synthesized DNA. In mammalian cells, this increment is achieved by enhanced transcription and 3' end processing. The non-polyadenylated histone mRNA 3' ends are generated by a unique mechanism involving the U7 small ribonucleoprotein (U7 snRNP).

The SERRATE protein is involved in alternative splicing in Arabidopsis thaliana.

How alternative splicing (AS) is regulated in plants has not yet been elucidated. Previously, we have shown that the nuclear cap-binding protein complex (AtCBC) is involved in AS in Arabidopsis thaliana. Here we show that both subunits of AtCBC (AtCBP20 and AtCBP80) interact with SERRATE (AtSE), a protein involved in the microRNA biogenesis pathway.

Regulation of plant gene expression by alternative splicing.

AS (alternative splicing) is a post-transcriptional process which regulates gene expression through increasing protein complexity and modulating mRNA transcript levels. Regulation of AS depends on interactions between trans-acting protein factors and cis-acting signals in the pre-mRNA (precursor mRNA) transcripts, termed 'combinatorial' control. Dynamic changes in AS patterns reflect changes in abundance, composition and activity of splicing factors in different cell types and in response to cellular or environmental cues.

Involvement of the nuclear cap-binding protein complex in alternative splicing in Arabidopsis thaliana.

The nuclear cap-binding protein complex (CBC) participates in 5' splice site selection of introns that are proximal to the mRNA cap. However, it is not known whether CBC has a role in alternative splicing. Using an RT-PCR alternative splicing panel, we analysed 435 alternative splicing events in Arabidopsis thaliana genes, encoding mainly transcription factors, splicing factors and stress-related proteins.

Plant mitochondrial genes can be expressed from mRNAs lacking stop codons.

The mRNAs of the nad6 and ccmC genes of Arabidopsis and cauliflower were found to be processed upstream of the inframe stop codons. This result was confirmed by northern hybridization and by RT-PCR. There is no evidence that an alternative stop codon is created post-transcriptionally, either by RNA editing or by polyadenylation.

[Family of pentatricopeptide repeat proteins].

PPR proteins belong to large family of nucleic acid binding proteins, mainly RNA-binding proteins. Their name is defined by the presence of so-called pentatricopeptide repeat (PPR), a degenerate 35-aminoacid repeats containing from 2 up to 26 such motifs arrayed in tandem of at least in one pair. PPR motif consists of two a helices A and B forming a superhelix enclosing a groove or tunnel which is likely to be the ligand-binding site.

Lupin nad9 and nad6 genes and their expression: 5' termini of the nad9 gene transcripts differentiate lupin species.

The mitochondrial nad9 and nad6 genes were analyzed in four lupin species: Lupinus luteus, Lupinus angustifolius, Lupinus albus and Lupinus mutabilis. The nucleotide sequence of these genes confirmed their high conservation, however, higher number of nucleotide substitution was observed in the L. albus genes.