CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly

Early spliceosome assembly requires phosphorylation of U1-70K, a constituent of the U1 small nuclear ribonucleoprotein (snRNP), but it is unclear which sites are phosphorylated, and by what enzyme, and how such modification regulates function. By profiling the proteome, we found that the Cdc2-like kinase 1 (CLK1) phosphorylates Ser-226 in the C terminus of U1-70K. This releases U1-70K from subnuclear granules facilitating interaction with U1 snRNP and the serine-arginine (SR) protein SRSF1, critical steps in establishing the 5′ splice site. CLK1 breaks contacts between the C terminus and the RNA recognition motif (RRM) in U1-70K releasing the RRM to bind SRSF1. This reorganization also permits stable interactions between U1-70K and several proteins associated with U1 snRNP. Nuclear induction of the SR protein kinase 1 (SRPK1) facilitates CLK1 dissociation from U1-70K, recycling the kinase for catalysis. These studies demonstrate that CLK1 plays a vital, signal-dependent role in early spliceosomal protein assembly by contouring U1-70K for protein–protein multitasking.

Edward Mills Purcell. 30 August 1912 — 7 March 1997

Professor Edward Purcell was a physicist of great distinction. With Felix Bloch he received the joint award of the Nobel Prize for Physics in 1952, for the developments respectively of nuclear magnetic resonance (NMR) and nuclear induction. In 1951, H.L. Ewen and Purcell (21)* detected radiation at the hydrogen hyperfine frequency of 1421 MHz coming from interstellar space, which created a new branch of astronomy. The Smith–Purcell effect (28) is now regarded as a potentially powerful source of radiation in the far infrared region of the spectrum. These were further achievements of prize–winning quality. Edward Mills Purcell was born in Taylorville, Illinois, USA, the son of Edward A. Purcell and Mary Elizabeth Mills, both natives of Illinois. From public schools in Taylorville and Mattoon, Illinois, he won a scholarship to Purdue University, Indiana. He graduated in 1933 in electrical engineering and published two papers (1, 2) on thin films with Professor K. Lark–Horowitz. Realizing that Purcell's gifts and interests lay in mathematics and physics, Lark–Horowitz invited him to take part in a research project on electron diffraction while he was still an undergraduate, and then recommended him for an exchange studentship in Germany. Purcell spent a year studying physics at the Technische Hochschule in Karlsruhe, with Professor W. Wenzel. On his return he entered Harvard University to work under J.H. Van Vleck (For.Mem.R.S. 1967; Nobel Laureate in Physics 1981). With Malcolm Hebb, who later became Director of Research at the Laboratories of the General Electric Company in Schenectady, New York, he made a theoretical study (3) of the properties of paramagnetic salts below 1 K. This publication was widely used for the interpretation of magnetic cooling experiments in low–ndash;temperature physics, including my own thesis work in 1937–39. Later, when I mentioned it, Purcell, always a modest man, said, ‘that was all Hebb’.

Groundwater NMR in conductive water

A surface method of groundwater prospecting using nuclear magnetic resonance (NMR) in the Earth’s magnetic field is under study. The technique is employed for hydrogeological surveys down to a depth of about 100 m. The advantage of this method is that an NMR signal can be observed only in the presence of groundwater. A circular wire loop with a diameter of 100 m is laid out on the ground to excite and receive the NMR signal. An oscillating current with a rectangular pulse‐shape is passed through the loop, with the carrier‐frequency being equal to the proton‐resonance frequency in the Earth’s field. The excitation pulse is followed by a nuclear induction emf caused by the free Larmor precession in the Earth’s field. Of practical importance is the effect of the electrical conductivity of the ground on a groundwater NMR survey. Finite‐ground conductivity can result in induced currents that can screen the NMR signal. The calculations of NMR signals are based on the transformation of Maxwell’s equations in terms of magnetic Hertz potentials through use of the reciprocity principle. Groundwater NMR is measured with an instrument designed at the Institute of Chemical Kinetics and Combustion, Russian Academy of Science, Novosibirsk. Experiments were conducted in the Altay region of Russia. Both NMR‐signal amplitude and phase, were measured and compared with the calculated results for horizontally stratified media. Borehole logs and vertical‐resistivity profiles were also used for evaluation of results. The conductivity is shown to affect both phase and amplitude of the NMR signal at resistivities of a few to a few tens of ohm‐m depending on the depth of the water‐saturated layers. There is good agreement between calculated and experimental data. It is also established that the measurements of only NMR amplitude and phase are not sufficient for determining groundwater salinity.

Magnetic Resonance Imaging

The first successful demonstration of the phenomenon of nuclear magnetic resonance (NMR), or nuclear induction in solids and liquids, was published almost simultaneously in 1946 by Bloch, Hansen, and Packard (7) working at Stanford University and Purcell, Torrey, and Pound (75) working at Harvard University. The immediate impact of their work was in physics and chemistry, but the applications have steadily widened and recently the application of NMR in medicine has become very exciting.