Johnny Sexton is out of Saturday’s opening Six Nations game against Scotland after aggravating his calf injury when trying to run on Monday.
The out-half did not train at Carton House this morning and has been ruled out of the Murrayfield encounter.
Paddy Jackson will now start Saturday's game having led the backline against South Africa last summer and in the Australia clash last November.
Ian Keatley, who still has not been announced as part of the squad, and Rory Scannell are in a two-way battle to cover from the bench.
Peter O'Mahony is also out of the game after suffering a hamstring injury, while Andrew Trimble is a major doubt after suffering a groin injury.
Forwards coach Simon Easterby confirmed the injury news but backed Jackson to thrive, while he added that he expects to see Sexton play in this year's Six Nations.
"Paddy has proven himself over a number of months, going back to the summer, that he can control the side and dictate the play. Johnny is one of the best 10s in the world, but we have to adapt," he said.
"That's the mark of this team, we can lose players in key positions and can adapt.
"With Johnny, it's purely now managing his return to training, that will take as long as it takes.
"There's no timescale, felt tightness yesterday and felt it was in Johnny's best interests not to push it.
"It's a case of monitoring or managing it.
"We've got Keats in with Paddy Jackson and Rory Scannell who has been slotting in at No 10, we feel we have enough cover in that position to make selections for this weekend.
"Whatever happens this weekend we'll make further assessments."