Forecasters have issued a fresh warning of persistent heavy snow for southern Scotland and north east England.
A Met Office amber “be prepared” alert is now in place from 21:00 on Wednesday until 05:00 on Thursday.
Hundreds of drivers who spent the night stranded on the main route between Scotland and England have resumed their journey.
Traffic Scotland said it was an improving picture on the M74 with vehicles moving, albeit slowly.
Public transport has been disrupted and schools will remain closed in parts of Scotland
More than 200 Scottish schools or nurseries are shut or partially closed, affecting more than 20,000 pupils.
The upgraded Met Office warning said travel delays were likely on roads with a risk that some vehicles and passengers could become stranded.
Delays or cancellations are likely to rail and air travel. Some rural communities are likely to become cut off and power cuts are “probable”.
Less severe yellow warnings remain in place with snow and ice forecast until Friday evening, with Scotland, Northern Ireland and the north of England likely to be affected.
The worst problems overnight were on the M74 in Lanarkshire and Dumfries and Galloway, with the motorway completely shut at times.
Mountain rescue teams were sent to help drivers trapped in cars at Millbank and Beattock, checking they were warm and had adequate supplies.
Disruption was also reported on the M62 trans-Pennine motorway, although by Wednesday morning traffic was able to move.
There have also been some school closures in Yorkshire. There are about 30 schools in Bradford which are to remain closed or have opened late.
Travel on the M74 was particularly difficult around junction 12 of the M74 in South Lanarkshire southbound and between junctions 14 and 15 northbound.
One driver stuck on the northbound carriageway of the M74, Fergus McCann, said the impatience of other drivers had made things worse.
He told the BBC: “There’s been a fair bit of impatient driving going on.
“People are in one queue, then people are cutting out and trying to go down lanes that clearly are not for driving on.
“It’s not a surprise that you’re getting a few hundred yards down the road and you’re seeing them facing the wrong way.”
Steve Harris became stranded on the M74 at 17:30 GMT and was still stuck between junctions 11 and 12 more than eight hours later.
“I’ve not moved really in the last four hours,” he told BBC Radio 5 live at about 03:00 GMT.
“I’ve managed to get out of my car a couple of times to stretch my legs. The snow is probably between four and six inches deep around the cars.”
Scotland’s transport minister, Humza Yousaf, apologised to motorists who had been stuck in their vehicles overnight, but insisted everything possible had been done to keep traffic moving.
He told the BBC’s Good Morning Scotland programmed: “We had hundreds of patrol vehicles and gritter vehicles out in the days before and during.”
Mr Yousaf said closing the motorway would have seen traffic diverted onto local roads, leading to pressure on those routes as well.
He said: “What we’re trying to do is to keep the traffic flow going. What happened last night was that as soon as a patch of road was cleared, it was very clear that as soon as people started moving they lost traction again.”
Responding to reports that some councils had already spent their winter roads budget, he said the Scottish government was willing to have a “conversation” with local authorities on the matter.
Several hundred schools across Scotland are closed because of the weather conditions.
Scottish Borders Council has said no schools will open in its area on Tuesday or Wednesday and 26 schools are shut in Dumfries and Galloway.
In the Highland Council area, more than 150 schools and nurseries are shut or partially closed, affecting 15,000 pupils.
Nearly 30 schools and nurseries are closed in South Lanarkshire and there are also a number of schools shut in East Ayrshire, Stirling, Falkirk and Perth and Kinross.
Snow was still a hazard on urban roads at the start of the rush hour.