Science - USA (2021-12-24)

CREDITS: (TOP TO BOTTOM HUANG

ET AL

.; DENNIS KUNKEL/MICROSCOPY/SCIENCE SOURCE

1572 24 DECEMBER 2021 • VOL 374 ISSUE 6575 science.org SCIENCE

pandemic. However, access

challenges remain, breakthrough

infections occur, and emerging

variants present increased risk.

Developing antiviral therapeu-

tics is therefore a high priority

for the treatment of COVID-19.

Some drug candidates in clinical

trials act against the viral RNA-

dependent RNA polymerase, but

there are other viral enzymes that

have been considered good tar-

gets for inhibition by drugs. Owen

et al. report the discovery and

characterization of a drug against

the main protease involved in the

cleavage of polyproteins involved

in viral replication. The drug,

PF-07321332, can be adminis-

tered orally, has good selectivity

and safety profiles, and protected

against infection in a mouse

model. In a phase 1 clinical trial,

ZEOLITES

Extra-large and

intersecting pores

Thermally stable zeolites with

large pores, such as zeolite

Y with 12-membered rings,

are used for converting large

molecules from petroleum into

smaller, more useful hydro-

carbons. Lin et al. report the

synthesis of ZEO-1, a thermally

stable zeolite with extra-large,

16-membered rings. The

use of tricyclohexylmethyl-

phosphonium as an organic

structure–directing agent

created a zeolite with a fully

interconnected multidimen-

sional framework and a very

high specific surface area.

—PDS

Science, abk3258, this issue p. 1605

NEURONAL SIGNALING

Gbg dimers get specific

at the synapse

In contrast to how much is

known about G protein–a

subunits, comparatively little

is known about G protein–bg

dimers, which regulate synaptic

transmission by inhibiting the

release of neurotransmitter-con-

taining vesicles from presynaptic

neurons. Yim et al. identified the

Gb and Gg subunits that inter-

acted with the SNARE complex,

which mediates vesicle exocyto-

sis. This analysis revealed that

the type of Gb and Gg subunits

that interacted with SNARE pro-

teins changed with epinephrine

stimulation and depended on the

type of neuron. —JFF

Sci. Signal. 14 , eabc4970 (2 021).

CORONAVIRUS

Path to another drug

against COVID-19

The rapid development of

vaccines has been crucial in

battling the ongoing COVID-19

False-color transmission electron

microscopy image of an excitatory

synapse showing vesicles primed

for exocytosis

Edited by Michael Funk

IN SCIENCE JOURNALS

RESEARCH

MOLECULAR BIOLOGY

A tunnel between RNA

polymerases

E

ukaryotes encode five multiple-subunit,

DNA-dependent RNA polymerases, of which

Pol I, Pol II, and Pol III function as single units

to produce cellular single-stranded RNA. The

plant-specific Pol IV forms a complex with

RDR2 (an RNA-dependent RNA polymerase) to

produce double-stranded precursors of small

interfering RNA essential for genomic DNA meth-

ylation. Huang et al. determined the cryo–electron

microscopy structures of the Pol IV-RDR2 com-

plex. The structures show that Pol IV and RDR2

connect their active centers through an inner RNA

transfer channel and that Pol IV reverses transcrip-

tion direction and hands over its transcript directly

through the channel to RDR2 for the production

of the second strand of the double-stranded RNA.

—DJ Science, abj9184, this issue p. 1579

A cryo–electron microscopy map reveals a molecule of

RNA (red) being transferred from one polymerase (green)

to the next (purple) through a protein channel.