Antibody reacting with lymphocyte surface immunoglobulin molecules induces these to gather over one pole of the cell. This suggests a possible mechanism for lymphocyte triggering by antigen and raises questions about cell membrane structure.

Redistribution and Pinocytosis of Lymphocyte Surface Immunoglobulin Molecules Induced by Anti-Immunoglobulin Antibody

The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells. Small double-stranded RNA molecules can efficiently trigger RNAi silencing of specific genes, but their therapeutic use has faced numerous challenges involving safety and potency. However, August 2018 marked a new era for the field, with the US Food and Drug Administration approving patisiran, the first RNAi-based drug. In this Review, we discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, the state of the current clinical pipeline and prospects for future advances, including novel RNAi pathway agents utilizing mechanisms beyond post-translational RNAi silencing.

The current state and future directions of RNAi-based therapeutics.

Ribonucleases H are enzymes that cleave the RNA of RNA/DNA hybrids that form during replication and repair and which could lead to DNA instability if they were not processed. There are two main types of RNase H, and at least one of them is present in most organisms. Eukaryotic RNases H are larger and more complex than their prokaryotic counterparts. Eukaryotic RNase H1 has acquired a hybrid binding domain that confers processivity and affinity for the substrate, whereas eukaryotic RNase H2 is composed of three different proteins: the catalytic subunit (2A), similar to the monomeric prokaryotic RNase HII, and two other subunits (2B and 2C) that have no prokaryotic counterparts and as yet unknown functions, but that are necessary for catalysis. In this minireview, we discuss some of the most recent findings on eukaryotic RNases H1 and H2, focusing on the structural data on complexes between human RNase H1 and RNA/DNA hybrids that had provided great detail of how the hybrid binding- and RNase H-domains recognize and cleave the RNA strand of the hybrid substrates. We also describe the progress made in understanding the in vivo function of eukaryotic RNases H. Although prokayotes and some single-cell eukaryotes do not require RNases H for viability, in higher eukaryotes RNases H are essential. Rnaseh1 null mice arrest development around E8.5 because RNase H1 is necessary during embryogenesis for mitochondrial DNA replication. Mutations in any of the three subunits of human RNase H2 cause Aicardi-Goutieres syndrome, a human neurological disorder with devastating consequences.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2009.06908.x

Ribonuclease H: the enzymes in Eukaryotes

In a discussion of the dynamics of protein folding two limiting models (random-search nucleation and chain propagation., diffusion–collision) are considered. It is suggested that the latter may have the dominant role in many proteins.

Protein-folding dynamics.

Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing

An enzyme present in extracts from calf thymus degrades specifically the RNA moiety of DNA-RNA hybrids. Other nucleic acids, such as single- or double-stranded DNA and single- or double-stranded RNA, are not affected to a comparable degree. If prepared free of the hybrid-degrading enzyme, RNA polymerase from calf thymus shows a fivefold increase in activity on denatured DNA as compared to native DNA.

https://science.sciencemag.org/content/sci/166/3903/393.full.pdf

Enzyme from Calf Thymus Degrading the RNA Moiety of DNA-RNA Hybrids: Effect on DNA-Dependent RNA Polymerase

Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids.

It is shown by isopycnic density gradient centrifugation that the DNAs of the sibling species Drosophila hydei, Drosophila neohydei and Drosophila pseudoneohydei differ regarding the numbers and proportions of satellite DNA bands. An overwhelming proportion of all repetitive nucleotide sequences of the DNA is contained in these satellite fractions. The majority of the satellites are species specific despite the close phylogenetic and cytological relationship between the three species studied. — By in situ hybridization experiments it is demonstrated that the various satellite sequences occupy different positions within the chromosomes. All types of localization patterns, from a wide spread occurrence in all chromosomes to an apparent restriction to kinetochore regions of single chromosomes, have been observed. Main band DNA, on the other hand, in its hybridization behavior reflects the DNA distribution according to the banding pattern in giant chromosomes. Generally satellite sequences seem to be included in α-heterochromatic chromosome regions but no relation to the heterochromatin of the Y-chromosome was found. — Renaturation studies support various evidence that satellite sequences occur in tandemly repetitious units. At least some of this repetitious material seems to be linked to non-satellite DNA sequences or to DNA of other satellites.

Repeated sequences in the DNA of Drosophila and their localization in giant chromosomes.

A large scale purification procedure of RNA polymerase from calf thymus is described. A factor stimulating synthesis of RNA by this enzyme has been extracted from the same tissue. Addition of the factor to the enzyme assay results in a 10-fold increased enzyme activity. This effect is only seen when native and not when denatured DNA is used as template. Several lines of evidence exclude trivial explanations of the stimulation effect and indicate a direct action of the factor on the enzyme. The active agent is probably a protein with a sedimentation constant of about 3 S.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1970.tb00286.x

A factor from calf thymus stimulating DNA-dependent RNA polymerase isolated from this tissue.

Conversion of uridine to UTP is enhanced in lymphocytes under the influence of phytohemagglutinin concomitant with the induction of uridine kinase. The uridine kinase activity in the induced cells decreases if the cells are treated with antibodies against phytohemagglutinin. The phosphorylation of uridine may be the limiting step in the incorporation of uridine into RNA. Uridine incorporation can thus not be taken as a direct measure of RNA synthesis.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1968.tb00226.x

Hans Stein

Papers

Enzyme from Calf Thymus Degrading the RNA Moiety of DNA-RNA Hybrids: Effect on DNA-Dependent RNA Polymerase

Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids.

Repeated sequences in the DNA of Drosophila and their localization in giant chromosomes.

A factor from calf thymus stimulating DNA-dependent RNA polymerase isolated from this tissue.

On the Synthesis of RNA in Lymphocytes Stimulated by Phytohemagglutinin